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2017


28.11.2017
Prof Ala-Korpela is giving a talk at the University of Queensland, Diamantina Institute (UQDI), Brisbane, Australia

Prof Ala-Korpela's talk is entitled Large-scale systems epidemiology – ­ recent applications and current trends. Prof Ala-Korpela's visit at the University of Queensland, Diamantina Institute is hosted by Prof David Evans.

27.11.2017
Prof Ala-Korpela is giving a talk at the Queensland Institute of Medical Research (QIMR Berghofer), Brisbane, Australia

Prof Ala-Korpela's talk is entitled Large-scale metabolic profiling and systems epidemiology – why and where are we? Prof Ala-Korpela's visit at the QIMR is hosted by Prof Nicholas Martin.

23.11.2017
Prof Ala-Korpela is giving a research seminar at the Monash University, Melbourne, Australia

Prof Ala-Korpela's seminar is entitled Large-scale systems epidemiology – recent applications and current trends. This is his first appearance at the Department of Epidemiology and Preventive Medicine at the Faculty of Medicine, Nursing and Health Sciences at Monash. Prof Ala-Korpela has been holding an adjunct Research Professor position in Systems Epidemiology in the Alfred Hospital at the Monash University since September 2017.

The seminar takes place in 553 St Kilda Road at 3 pm.

16.11.2017
2 Postdoctoral positions in Systems Epidemiology

A global setting (Oulu-Bristol-Melbourne) for international and multidisciplinary science

The Computational Medicine Research Team invites highly motivated individuals to apply for postdoctoral positions at the University of Oulu, Finland. These positions are initially for 2 years with a broad focus on systems epidemiology, i.e., integration of multi-omics approaches and data in epidemiology and genetics. Potential extensions are possible for successful candidates. We would also be interested in discussing with candidates at assistant or associate professor level. We can offer these positions 1.1.2018 onwards and would hope successful candidates to start no later than in March 2018.

These positions and the work to be done are part of our global endeavour aiming to understand and improve cardiometabolic risk assessment by conducting high-throughput multi-omics profiling of extensive population cohorts and trials at unprecedented sample-sizes. Large-scale studies are a prerequisite for statistically sound metabolic stratifications as well as for understanding the (patho)physiological function of potential new disease biomarkers and the causal pathways in disease aetiology with the aid of modern genetic data. Please see the following recent papers to understand our thinking; PubMed PMID numbers: 29106475, 29038155, 28569269, 27955712, 27789667, 27005778 and 27989323.

We expect you to have a PhD degree in Bioengineering, Biochemistry, Analytical Chemistry, Medical Sciences, Statistics, Epidemiology, or in a related area. You would need to have good skills in written and spoken English. Knowledge of medical & epidemiological statistics and skills to use R would be essential. A few international peer-reviewed publications in good journals would also be a prerequisite for these positions.

We are offering an international, dynamic working environment in which quality and professionalism are encouraged. We have extensive international collaboration and are tightly connected to the UK epidemiology community (mainly University of Bristol, University of Oxford and University of Cambridge) and Australia (Baker Heart and Diabetes Institute & Monash University). Depending on the scientific project, mobility between relevant research sites would be encouraged.

In Oulu we have light summers and snowy winters, cooperative and competent people, active development, and high-class public services. University of Oulu offers an excellent setting for study, work, research and personal development.

Enthusiastic candidates are encouraged to contact Prof Ala-Korpela (mika.ala-korpela@oulu.fi) or Dr Kettunen (johannes.kettunen@oulu.fi) for further information. Informal applications can be sent to the above email addresses; this call closes on Friday 15.12.2017, at 24.00 (midnight, Finnish local time) but we reserve the right to fill the positions before this deadline.

13.11.2017
Prof Ala-Korpela gives an invited talk at the American Heart Association Scientific Meeting in Anaheim, CA

Prof Ala-Korpela's talk at AHA is entitled NMR based lipidomics in cardiovascular risk. The talk is in PR.CVS.2305 (Room 26 - Prevention Health and Wellness; 2:00 pm - 3:15 pm). The Session is entitled "The current state of lipidomic biomarkers for cardiovascular risk". This cardiovascular seminar is moderated by A/Prof Peter Meikle (Melbourne, Australia) & Dr Jeff Meeusen (Rochester, MN). Other presenters are Dr Ioanna Tzoulaki (London, UK), Prof Manuer Mayr (London, UK) and A/Prof Peter Meikle.

This talk will be given by Dr Michael V Holmes, University of Oxford, UK.

11.10.2017
Prof Ala-Korpela relocates to the Baker Heart and Diabetes Institute in Melbourne, Australia

Prof Ala-Korpela has recently been granted a Distinguished Talent visa to Australia. This seals his contract with the Baker Heart and Diabetes Institute in Melbourne, Australia. Prof Ala-Korpela will lead a new Systems Epidemiology Laboratory at the Baker Institute and will also have strong links to the Department of Epidemiology and Preventive Medicine in the Faculty of Medicine, Nursing and Health Sciences at Monash University, with an adjunct position as Research Professor in Systems Epidemiology.

The Baker Heart and Diabetes Institute is an independent, internationally renowned medical research facility, with a history spanning more than 90 years. Its research is dedicated to the prevention, diagnosis and treatment of cardiovascular disease, diabetes and obesity. These are today's biggest health challenges facing Australians and people globally.

The Baker Institute is one of the few institutes in the world where the work of staff spans benchtop to bedside and where research is dedicated to tackling the deadly trio of diseases: cardiovascular disease, diabetes and obesity. The Institute has 30 laboratories comprising more than 300 researchers, clinicians and research nurses, support staff and students who work across five research areas: Basic, Translational and Clinical Research as well as Population and Aboriginal Health. The new Systems Epidemiology Laboratory will form part of the Population Health Domain.

More information about the Baker Heart and Diabetes Institute can be found on their website and in their Impact Reports.

Prof Ala-Korpela will be starting at the Baker Heart and Diabetes Institute in January 2018. He will be maintaining strong links to the remaining Computational Medicine Research Team at the University of Oulu, Finland, the NMR Metabolomics Laboratory at the University of Eastern Finland, Kuopio, Finland and the MRC Integrative Epidemiology Unit at the Bristol Medical School, University of Bristol, UK

Prof Ala-Korpela's relocation to Australia will add on to the already extensive international flavour of his research coalition and is expected to give great global opportunities to all involved: "to understand and efficiently prevent and treat common global diseases, we need to take universal actions".

5.9.2017
Dr Qin Wang awarded a 4-year Postdoctoral Fellowship in Endocrinology and Metabolism by the Novo Nordisk Foundation for a scientific collaboration project between the University of Oulu, Finland and the Baker Heart and Diabetes Institute, Melbourne, Australia

Dr Wang is a talented 31 years young scientist who recently got her PhD from the University of Oulu. Her thesis was entitled Epidemiological applications of quantitative serum NMR metabolomics: causal inference from observational studies. She has continued her work in the Computational Medicine Research Team and has recently been working with the potential causal role of insulin resistance for circulating amino acids and with the metabolic characterisation of menopause. Her personal profile and publications can be found here.

Dr Wang’s Fellowship project is entitled Epidemiological applications of quantitative serum metabolomics - integration of NMR metabolomics and MS lipidomics. The grant from the Novo Nordisk Foundation is in total DKK 4,000,000 ie approximately 540,000 €, including Dr Wang’s salary and various travel and research costs for the period of Jan 2018 - Dec 2021.

Metabolic profiling is increasingly used in epidemiology. Extensive molecular coverage enables detailed molecular understanding of health and disease and identification of novel biomarkers. In this project Dr Wang aims to expand the molecular coverage by integrating serum NMR metabolomics and MS lipidomics. A world-leading MS lipidomics platform, distinctive to warrant large-scale quantitative experimentations, has been developed at the Baker Heart and Diabetes Institute, Melbourne, in the lead of A/Prof Peter Meikle. A recent review by A/Prof Meikle’s team on Lipidomic Analyses in Epidemiology can be found in the International Journal of Epidemiology. Baker is also a prestigious institute in diabetes and cardiometabolic research and thereby provides a unique and ideal environment for this project. The integration of two complementary quantitative technologies leads to almost 1000 metabolic measures, providing an unprecedented metabolic characterization of an individual’s metabolic status. The serum NMR metabolomics platform to be applied is developed in the Computatational Medicine Research Team at the University of Oulu and the University of Eastern Finland in the lead of Prof Mika Ala-Korpela. This NMR platform is particularly designed for high-throughput and has already been widely used in large-scale epidemiology and genetics - recent reviews on the NMR methodology can be found in Circulation Cardiovascular Genetics and in the American Journal of Epidemiology. On the other hand, large-scale applications of MS lipidomics are still at their infancy.

During the Fellowship Dr Wang will focus on appling MS lipidomics in multiple prospective population cohorts with clearly more than 10,000 individuals for whom both NMR and genome-wide data are already available. She will conduct a genome-wide analysis study of MS lipidomics to define the genetic architecture of the human lipidome and aims to assess potential causal effects of lipid biomarkers on cardiometabolic diseases via Mendelian randomization. In addition, she is going to assess the potential causal effects of common therapies and established risk markers on the lipidome and to integrate NMR metabolomics and MS lipidomics to study the molecular trajectory through disease development to disease progression. These objectives are likely to provide a comprehensive understanding of the causal chain through risk markers to circulating biomarkers and eventually to disease endpoints. The epidemiological findings of this project are expected to be unparalleled and they are likely to deepen our molecular and causal understanding of cardiometabolic diseases. It is likely that the results will also provide multiple translational corollaries.

The Baker Heart and Diabetes Institute is an independent, internationally renowned medical research facility, with a history spanning more than 90 years. Its contributions in the field of diabetes have ranged from the initial descriptions of type 1 and type 2 diabetes in the mid-20th century (Bornstein J, BMJ 1951), to leading population work from the AusDIAB study, which foreshadowed the current diabetes epidemic (Dunstan, D et al. Diabetes Care 2002). Baker is among the 5 largest medical research institutes in Australia, and the only one with a mission to reduce death and disability from cardiovascular disease, diabetes and related disorders. The work at Baker extends from the laboratory to wide-scale community studies with a focus on diagnosis, prevention and treatment of diabetes and cardiovascular disease. The Baker scientists teach and collaborate with colleagues across the world and Baker is the home to scientists from in Europe, the Americas and Asia – appropriately so, because these two prevalent and complex diseases are responsible for the most deaths and the highest health costs in the world. The comprehensive range of research undertaken to target these deadly diseases, combined with the flexibility and innovation to respond to changing health and community needs, is unique and sets the Baker Institute apart from other health and research Institutes. The Institute is well positioned to address these challenges. The Institute's highly diverse team includes cardiologists, diabetes physicians, bench-top scientists, epidemiologists, dieticians, psychologists, nurse educators, renal specialists and physical activity experts. Together, they are working to translate laboratory findings into new approaches to prevention, treatment and care.

Dr Wang and A/Prof Meikle captured in planning on the beach in Melbourne in February 2017.
15.5.2017
Dr Ohukainen is giving an invited talk at the annual meeting of the National Association of Information Studies

The talk is titled “Tutkijana sosiaalisen median pyörteissä” (”Scientist in the vortex of social media”) and the topic is the use of various social media platforms as tools for professional networking as well as popularizing science to lay audiences. Dr Ohukainen is speaking both from personal experience as well as some of the research that’s been done on the subject. The meeting is titled “Totuuden jälkeinen aika?” (“Age of post-truth?”) and it covers timely topics like fake news/media, “alternative facts” and opinions vs. scientific facts. The meeting takes place on Monday 15th of May at 12-16 o’clock at LeaForum, University of Oulu.

The event is open for everyone and more information can be found here: http://www.oulu.fi/informaatiotutkimus/node/46210 https://www.facebook.com/events/283366968785983/

4.4.2017
Prof Ala-Korpela is giving a talk at the Baker Heart and Diabetes Institute, Melbourne, Australia

Prof Ala-Korpela’s talk is entitled Large-scale systems epidemiology – lipids and lipoproteins, and something about causality and translational issues. Prof Ala-Korpela’s visit and talk at the Baker Institute relates to planned forthcoming extensive scientific collaboration.

31.3.2017
Prof Ala-Korpela is giving an invited talk at the Finnish Cardiology Society Meeting

Prof Ala-Korpela is giving an invited talk, entitled Lipidomiikka, lipoproteiinien alaluokat ja metabolinen profilointi ­– epidemiologian uudet tuulet, at the Finnish Cardiology Society Spring Meeting 29.-31.3.2017 in Kuopio, Finland. The talk will be given in Finnish and it will be on Friday 31st March at 10:20 am.

The meeting program can be found here.

24.3.2017
Dr Kettunen funded for 5 years from the Novo Nordisk Foundation Excellence Grant for Young Researchers within Endocrinology and Metabolism

Novo Nordisk Foundation is funding a project, entitled HDL-mediated cholesterol efflux capacity - epidemiology, genetics and causality in cardiometabolic diseases, for 5 years (May 2017 – April 2022). The total sum of the grant is DKK 4,941,200 ie approximately 665,000 €.

High-density lipoprotein cholesterol (HDL-C) has been traditionally viewed as the “good cholesterol” because if it is low, risk of heart disease is increased. Albeit HDL-C has been deemed as a non-causal for risk, recent studies have demonstrated that the functional properties of HDL particles are important; one of these functions is HDL-mediated cholesterol efflux capacity (HDL-CEC). HDL-CEC has been shown to be a predictor of incident cardiovascular endpoints independent of traditional risk factors, HDL-C and apolipoprotein A-I. However, the replication and characterization of HDL-CEC with standard risk factors in large population samples is missing due to laborious and costly in vitro methodology needed for the traditional measurements. To overcome this limitation, a unique high-throughput method for determining HDL-CEC has been developed in our team. This novel methodology allows determination of HDL-CEC in high-throughput, cost-effective manner. The purpose of this interdisciplinary project is 1) to fine-tune the novel HDL-CEC measurements for specific efflux pathways and 2) to combine HDL-CEC with epidemiology and genetics in large population samples. The results will inform on the relationship between traditional cardiometabolic risk factors and HDL-CEC as well as on the predictive capability of HDL-CEC for multiple cardiometabolic endpoints, including type 2 diabetes. A genome-wide association study will elucidate the underlying biology of HDL-CEC and the genetic results will be used to determine the potential causality between cholesterol efflux and cardiometabolic disease endpoints in a Mendelian randomization framework. The genetic results will also allow us to study the effect of existing (and emerging) drug treatments on cholesterol efflux.

Dr Kettunen is a Docent in Genetics from the University of Helsinki. He joined the Computational Medicine Research Team, as the Head of Genetics and a Team Leader, January 2014. He was awarded a 5-year Academy of Finland Research Fellow position from September 2016 onwards. He is also one of the principal investigators at the Biocenter Oulu (2016-). He has recently led several key papers in the area of systems epidemiology, for example:

AV Ahola-Olli, P Würtz, AS Havulinna, K Aalto, N Pitkänen, T Lehtimäki, M Kähönen, LP Lyytikäinen, E Raitoharju, I Seppälä, AP Sarin, S Ripatti, A Palotie, M Perola, JS Viikari, S Jalkanen, M Maksimow, V Salomaa, M Salmi, J Kettunen, OT Raitakari Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors American Journal of Human Genetics 100, 40-50, 2017

J Kettunen, A Demirkan, P Würtz, HHM Draisma, T Haller, R Rawal, A Vaarhorst, AJ Kangas, LP Lyytikäinen, M Pirinen, R Pool, AP Sarin, P Soininen, T Tukiainen, Q Wang, M Tiainen, T Tynkkynen, N Amin, T Zeller, M Beekman, J Deelen, KW van Dijk, JJ Hottenga,EM van Leeuwen, T Lehtimäki, E Mihailov, RJ Rose, AJM de Craen, C Gieger, M Kähönen, M Perola, Blankenberg S, Savolainen MJ, Verhoeven A, Viikari J, Willemsen G, Boomsma DI, van Duijn CM, Eriksson J, Jula A, Järvelin MR, Kaprio J, Metspalu A, Raitakari O, Salomaa V, PE Slagboom, M Waldenberger, S Ripatti, M Ala-Korpela Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA Nature Communications 7, 11122, 2016

SC Ritchie, P Würtz, AP Nath, G Abraham, AS Havulinna, LG Fearnley, A-P Sarin, AJ Kangas, P Soininen, K Aalto, I Seppälä, E Raitoharju, M Salmi, M Maksimow, S Männistö, M Kähönen, M Juonala, S Ripatti, T Lehtimäki, S Jalkanen, M Perola, O Raitakari, V Salomaa, M Ala-Korpela, J Kettunen, M Inouye The biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection Cell Systems 1, 293-301, 2015

More about him and his publications can be found here: http://computationalmedicine.fi/teamandorganisation#kettunen

23.3.2017
Researcher Qin Wang's PhD-thesis and -defence

MSc Wang will defend her PhD-thesis, entitled Epidemiological applications of quantitative serum NMR metabolomics: causal inference from observational studies, in Auditorium P117 (Aapistie 5B, Oulu), on 23 March 2017, at 12 noon. The thesis can be found at http://jultika.oulu.fi/Record/isbn978-952-62-1508-2; the abstract is given below.

Abstract
Cardiovascular diseases are the leading cause of death worldwide and type 2 diabetes is reaching a global epidemic. Epidemiological studies have identified numerous risk factors and pharmacotherapies in relation to these cardiometabolic diseases. However, the detailed molecular mechanisms of these risk factors and drug therapies generally remain incompletely understood. Elucidating the underlying molecular effects would be essential for better understanding of the disease pathogenesis and also for discovering new therapeutic targets. Quantitative serum metabolomics, which allows for simultaneous quantification of multiple circulating metabolic measures, provides a hypothesis-free approach to systematically inspect the metabolic changes in response to endogenous and exogenous stimuli. Metabolomics thus presents a valuable tool to study the detailed molecular effects of disease risk factors and drug therapies. However, current metabolomics studies are mostly conducted in small cross-sectional studies and the causal relations of the risk factors on the metabolic measures are generally unclear, providing limited public health impact. The present thesis serves as a proof-of-concept to illustrate that well-designed observational studies can be used to infer causality. With the exemplars of assessing molecular effects of two risk factors (body mass index and sex hormone-binding globulin) and two drug therapies (statins and oral contraceptives), the thesis demonstrates that an improved causal inference can be achieved in observational studies via the combination of multiple study designs, including cross-sectional, longitudinal and Mendelian randomization analysis. This robust study design approach together with metabolomics data can be also extended to study the molecular effects of other risk factors and drug therapies. With an improved molecular understanding of a wide range of risk factors and therapies, better understanding of disease pathogenesis is ensured.

20.3.2017
Prof Ala-Korpela is giving a research seminar at the Turku PET Centre, University of Turku

Prof Ala-Korpela is giving a research seminar, entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects, at the Turku PET Centre, University of Turku. This talk is also part of the LIFESPAN (Lifespan of Cardiovascular, Inflammatory, Endocrine & Metabolic Disorders) seminar series.

3.3.2017
Prof Ala-Korpela is giving a talk at the SAHMRI in the Heart Health seminar / University of Adelaide, Australia

Prof Ala-Korpela is giving a research seminar, entitled Lipoprotein subclasses and their contrasting causal roles in coronary heart disease, at the South Australian Health and Medical Research Institute (SAHMRI) in Adelaide, Australia. The talk is part of the Heart Health seminar series.

2.3.2017
Prof Ala-Korpela is giving a talk at the Future Industries Institute, University of South Australia

Prof Ala-Korpela's talk at the Future Industries Institute is entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects. The seminar is scheduled to start at 1 pm in seminar room MM1-05 in the Future Industries Institute, MM Building on Mawson Lakes Campus of the University of South Australia, Adelaide.

24.2.2017
Prof Ala-Korpela is giving a talk at the Baker Heart and Diabetes Institute, Melbourne, Australia

Prof Ala-Korpela's talk is entitled Quantitative metabolomics in large-scale epidemiology – where are we and (when) will translation emerge? This presentation is part of the 2017 Baker Heart and Diabetes Institute Friday seminar program.

21.2.2017
Prof Ala-Korpela is giving a talk at the University of South Australia, City East Campus, Adelaide, Australia

Prof Ala-Korpela is giving a talk, entitled Systemic metabolic effects of drinks, drugs & babies – large-scale metabolomics applications in observational epidemiology, in the Quality Use of Medicines and Pharmacy Research Centre's Research Seminar at the University of South Australia, City East Campus, Adelaide, Australia. The talk takes place at 11 am at 3 Reid Building, Frome Rd.

13.2.2017
Prof Ala-Korpela is giving a research seminar at the Department of Medicine and Therapeutics, Chinese University of Hong Kong

Prof Ala-Korpela is giving a research seminar, entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects, at the Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin.

23.1.2017
The Computational Medicine Research Team published 4 articles and an editorial in the same issue of International Journal of Epidemiology

The researchers in the Computational Medicine Research Team recently published four articles and an editorial in a themed issue of International Journal of Epidemiology (IJE) on Metabolic Phenotyping in Epidemiology. The issue was co-edited by Prof. Ala-Korpela and Prof. George Davey Smith (University of Bristol, UK). IJE is a highly-ranked, leading journal in the field of epidemiology research.

The articles with links are listed below. Of the original research articles those marked with red color were led or co-led by the Computational Medicine Research Team.

M Ala-Korpela, G Davey Smith Metabolic profiling ­– multitude of technologies with great research potential, but (when) will translation emerge? (Editorial for the Themed Issue on Metabolic Phenotyping in Epidemiology) International Journal of Epidemiology 45, 1311-1316, 2016

P Würtz, S Cook, Q Wang, M Tiainen, T Tynkkynen, AJ Kangas, P Soininen, J Laitinen, J Viikari, M Kähönen, T Lehtimäki, M Perola,S Blankenberg, T Zeller, S Männistö, V Salomaa, M-R Järvelin, OT Raitakari, M Ala-Korpela, DA Leon Metabolic profiling of alcohol consumption in 9778 young adults International Journal of Epidemiology 45, 1493-1506, 2016

Q Wang, P Würtz, K Auro, L Morin-Papunen, AJ Kangas, P Soininen, M Tiainen, T Tynkkynen, A Joensuu, AS Havulinna, K Aalto, M Salmi, S Blankenberg, T Zeller, J Viikari, M Kähönen, T Lehtimäki, V Salomaa, S Jalkanen, M-R Järvelin, M Perola, OT Raitakari, DA Lawlor, J Kettunen, M Ala-Korpela Effects of hormonal contraception on systemic metabolism: Cross-sectional and longitudinal evidence International Journal of Epidemiology 45, 1445-1457, 2016

S Vogt, S Wahl, J Kettunen, S Breitner, G Kastenmüller, C Gieger, K Suhre, M Waldenberger, J Kratzsch, M Perola, V Salomaa, S Blankenberg, T Zeller, P Soininen, AJ Kangas, A Peters, H Grallert, M Ala-Korpela, B Thorand Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D ­ A cross-sectional analysis in population-based data International Journal of Epidemiology 45, 1469-1481, 2016

P Würtz, Q Wang, M Niironen, T Tynkkynen, M Tiainen, F Drenos, AJ Kangas, P Soininen, MR Skilton, K Heikkilä, A Pouta, M Kähönen, T Lehtimäki, RJ Rose, E Kajantie, M Perola, J Kaprio, JG Eriksson, OT Raitakari, DA Lawlor, G Davey Smith, M-R Järvelin, M Ala-Korpela, K Auro Metabolic signatures of birth weight in 18 288 adolescents and adults International Journal of Epidemiology 45, 1539-1550, 2016

Prof. Ala-Korpela’s recent Blog about the themed issue can be found at https://ije-blog.com/2017/01/19/metabolic-phenotyping-in-epidemiology-2/


This news was originally published by Biocenter Oulu on 20.1.2017
http://www.oulu.fi/biocenter/node/44337

12.1.2017
Prof Ala-Korpela is giving a research seminar at the University of Valencia, Spain

Prof Ala-Korpela's talk is entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects. He will also visit the Health Research Institute INCLIVA, the local metabolomics laboratory and meet various clinical researchers from the University Clinical Hospital of Valencia.

10.1.2017
Prof Ala-Korpela is giving a research seminar at Universitat Rovira i Virgili in Tarragona, Spain

Prof Ala-Korpela's talk is entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects. He will also visit the Centre for Omic Sciences (COS) in Reus.

1.1.2017
Dr Würtz starts a research group at the University of Helsinki

Dr Peter Würtz is starting a research group at the University of Helsinki, Faculty of Medicine. Peter was a member of the Computational Medicine Research Team since early 2009, i.e., almost 8 years. During this time Peter became an internationally leading scientist in molecular epidemiology, particularly in applying quantitative high-throughput metabolomics in large-scale population-based cohorts and studies. Peter published some 40 peer-reviewed articles in key international journals in this area, being the first author in several seminal contributions in the field, for example:

P Würtz, Q Wang, P Soininen, AJ Kangas, G Fatemifar, T Tynkkynen, M Tiainen, M Perola, T Tillin, AD Hughes, P Mäntyselkä, M Kähönen, T Lehtimäki, N Sattar, AD Hingorani, J-P Casas, V Salomaa, M Kivimäki, M-R Järvelin, G Davey Smith, M Vanhala, DA Lawlor, OT Raitakari, N Chaturvedi, J Kettunen, M Ala-Korpela Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase JACC – Journal of the American College of Cardiology 67, 1200-1210, 2016

P Würtz, AS Havulinna, P Soininen, T Tynkkynen, D Prieto-Merino, T Tillin, A Ghorbani, A Artati, Q Wang, M Tiainen, AJ Kangas, J Kettunen, J Kaikkonen, V Mikkilä, A Jula, M Kähönen, T Lehtimäki, DA Lawlor, TR Gaunt, AD Hughes, N Sattar, T Illig, J Adamski, TJ Wang, M Perola, S Ripatti, RS Vasan, OT Raitakari RE Gerszten, JP Casas, N Chaturvedi, M Ala-Korpela, V Salomaa Metabolite profiling and cardiovascular event risk: a prospective study of three population-based cohorts Circulation 131, 774-785, 2015

P Würtz, Q Wang, AJ Kangas, RC Richmond, J. Skarp, M Tiainen, T Tynkkynen, P Soininen, AS Havulinna, M Kaakinen, JS Viikari, MJ Savolainen, M Kähönen, T Lehtimäki, S Männistö, S Blankenberg, T Zeller, J Laitinen, A Pouta, P Mäntyselkä, M Vanhala, P Elliott, KH Pietiläinen, S Ripatti, V Salomaa, OT Raitakari, MR Järvelin, G Davey Smith, M Ala-Korpela Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change PLoS Medicine 11, e1001765, 2014

P Würtz, V-P Mäkinen, P Soininen, A J Kangas, T Tukiainen, J Kettunen, M J Savolainen, T Tammelin, J S Viikari, T Rönnemaa, M Kähönen, T Lehtimäki, S Ripatti, O T Raitakari, M-R Järvelin, M Ala-Korpela Metabolic Signatures of Insulin Resistance in 7,098 Young Adults Diabetes 61, 1372-1380, 2012

P Würtz, J R Raiko, C G Magnussen, P Soininen, A J Kangas, T Tynkkynen, R Thomson, R Laatikainen, M J Savolainen, J Laurikka, P Kuukasjärvi, M Tarkka, P J Karhunen, A Jula, J S Viikari, M Kähönen, T Lehtimäki, M Juonala, M Ala-Korpela, O T Raitakari High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis European Heart Journal 33, 2307-2316, 2012

The Team greatly acknowledges Peter’s enthusiastic contributions to the science and also his personally great interactive spirit. We wish Peter all the best with his endeavours in his new team at the University of Helsinki and wish to maintain an active collaboration with him.

2016


5.12.2016
Dr Würtz is giving a talk at the EMBL–Wellcome Conference in Heidelberg, Germany

Dr Würtz is giving a talk at the EMBL–Wellcome Conference on Target Validation using Genomics and Informatics in Heidelberg, Germany, on Monday 5th December 2016. The talk is entitled Metabolomic Screening of Cholesterol Lowering Targets: Comprehensive Metabolic Effects of Statins, Ezetimibe and PCSK9-inhibition Assessed via Genetic Evidence in 30,000 individuals.

Programme

17.11.2016
Prof Ala-Korpela is giving a research seminar at the University of Hong Kong

Prof Ala-Korpela is giving a research seminar, entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects, at the University of Hong Kong, Faculty of Medicine, School of Biomedical Sciences.

Date: November 17, 2016
Time: 4:30 pm
Venue: Lecture Theatre 2 (LT2)
Cheung Kung Hai Conference Centre
Faculty of Medicine Building, 21 Sassoon Road Pokfulam
Hong Kong

15.11.2016
Dr Würtz is giving 2 talks at the American Heart Association Sessions in New Orleans

Dr Würtz is giving two talks at the American Heart Association Sessions in New Orleans on Tuesdat 15th November 2016. The talks are Metabolomic Effects of Statin Therapy, Ezetimibe and PCSK9-Inhibition: Comparison by Genetic Evidence (12:30 PM ) and Metabolomics of Non-alcoholic Fatty Liver Disease in Young Adults Reveals Pronounced Metabolic Deviations Prior to Disease Onset ( 4:30 PM).

Please see more here.

11.11.2016
Prof Ala-Korpela is giving a seminar at the SAHMRI / University of Adelaide, Australia

Prof Ala-Korpela is giving a research seminar, entitled Quantitative serum metabolomics in large-scale systems epidemiology - recent progress & translational aspects, at the South Australian Health and Medical Research Institute (SAHMRI) in Adelaide, Australia.

10.11.2016
Eden Hills Science Day at the SAHMRI / University of Adelaide, Australia

Prof Ville-Petteri Mäkinen and his research team are organising a Science Day at the SAHMRI / University of Adelaide, Australia together with Prof Peter Meikle (University of Melbourne, Australia) and Prof Mika Ala-Korpela. The program is below showing the attending team members and topics of the talks.

25.10.2016
Short course in Metabolomics in Epidemiology at the University of Bristol

Course dates: 26-27 October 2016.
Course duration: 2 days (approximately 11 hours of lectures and 3 hours of practicals).
Course tutors: Professor Mika Ala-Korpela (course organiser), Professor Debbie Lawlor, Dr Peter Würtz, Dr Pasi Soininen, Antti Kangas & Qin Wang.
Organised by the School of Social and Community Medicine at the University of Bristol.
This year the course is kept as a pilot for invited University of Bristol staff, postgraduate students and selected collaborators.

Course aims and objectives
This course is an introductory course on omics sciences, particularly quantitative metabolomics, and their current and future role in epidemiology and medicine. It is aimed at familiarising participants with the basis and applications and integration of various omics disciplines. The focus will be in quantitative metabolomics, but a brief introduction, e.g., to genomics and transcriptomics will be given in the light of integration of multiple omics data sets and domains in systems epidemiology research. An overview on experimental issues as well as data characterisation and analyses is given with respect to key quantitative NMR and mass spec metabolomics methodologies. The focus is on the role of metabolomics and its applications, but in general systems epidemiology thinking remains on the background with an emphasis on understanding the relation between various omics spaces and the importance of their integration in modern epidemiology. The concept of "big data" will be introduced in relation to systems epidemiology and medicine. The role and concept of biobanking will be introduced and linked with electronic health records. Several exemplars of the above mentioned concepts are illustrated in real epidemiological research applications, including genetic background of systemic metabolism (so-called genome-wide association study approach) and how genetics, metabolomics and big data can enhance drug development.

Please see more at http://www.bristol.ac.uk/social-community-medicine/shortcourse/metabolomics-in-epidemiology/.

10.-11.10.2016
UK Wellcome Trust Hinxton Retreat on Defining the UK Roadmap for Biomedical Metabolic Phenotyping

Hinxton Retreats, held at Wellcome Genome Campus at Cambridge, are funded by UK Wellcome Trust. The are meant to be discussion of emerging, forward-looking and exciting areas of scientific and technical interest, including associated policy issues. Each meeting aims to be the best overall meeting in its field ­ the name "Hinxton Retreat" should be synonymous with quality meetings. The meetings are invitation-only, closed meetings for a maximum of 40 carefully chosen participants. The meetings have emphasis on an informal and relaxed environment to encourage intense debate and discussion rather than a series of "standard presentations". The organizers must write a meeting report for Wellcome Trust and publication of review articles or other papers that synthesize the main discussions at the Retreat are encouraged.

Prof Ala-Korpela was invited by the Wellcom Trust as one of the Scientific Programme Committee Members for the Hinxton Retreat on Defining the UK Roadmap for Biomedical Metabolic Phenotyping. Other Committee Members were:
Prof Jeremy Nicholson, Chair in Biological Chemistry, Imperial College London
Prof Valerie O'Donnell, Chair in Biochemistry, Cardiff University
Prof Naveed Sattar, Chair in Metabolic Medicine, University of Glasgow
Prof Mark Viant, Chair in Metabolomics, University of Birmingham
Dr Danielle Cannon, Wellcome Trust

Prof Ala-Korpela's presentation in the Retreat was entitled Quantitative serum metabolomics in large-scale epidemiology. He also chaired a session entitled Unmet biomedical challenges and associated technology needs.

In total the Retreat had around 40 attendees. Key invited and attending scientists were, for example:
Prof Manuel Mayr, Kings College London
Prof Debbie Lawlor, University of Bristol
Prof George Davey Smith, University of Bristol
Prof Paul Elliott, Imperial College London
Prof Diana Kuh, UCL
Prof Zhengming Chen, University of Oxford
Prof Aroon Hingorani, UCL

The UK has played a significant leadership role in the emergence and growth of metabolic phenotyping (used here to include the terms metabolomics, metabonomics and lipidomics), in particular its applications to basic biomedical research, clinical studies and epidemiology. Multiple high profile projects have been conducted, including through partnerships between universities and industry, which have driven the field globally. Many opportunities remain for the UK to retain this leadership role, in part through co-ordinating activities strategically. Hence the central theme of the retreat was to bring together the relevant experts ­ across multiple disciplines including technologists, computational biologists, basic biomedical researchers, epidemiologists and clinicians ­ to determine the short and longer term needs of the community and in particular to identify some of the opportunities and grand challenges in biomedical metabolic phenotyping.

Active discussions focused around the needs of the epidemiology community, in particular the degree to which non-targeted spectroscopic and spectrometric based metabolomics approaches can provide relevant data. Some of the epidemiologists attending highlighted the following concerns: overtraining of classification models with high numbers of variables, cross-sectional study settings with small numbers of individuals, no independent (biological) replication and inadequate attention to confounding variables. It was stated by some that were present that for metabolomics to have a meaningful role in epidemiology, quantitative molecular data, i.e., identified molecular concentrations, should be provided by the metabolomics methodologies. Furthermore, to facilitate a shift towards addressing clinically important questions, tighter collaborations with clinicians in appropriately large study cohorts and trials are needed. Large-scale epidemiological cohorts and biobanks (like the UK Biobank and the China Kadoorie Biobank) were noted as very important from the basic (epidemiological) science point of view. The discussions also highlighted that misunderstandings exist between the "metabolomics" and "epidemiology" fields and showed a need for truly multidisciplinary research coalitions to advance towards useful applications in epidemiology. These multidisciplinary research coalitions should work together both in method development and in epidemiological applications ­ e.g., methods development should incorporate epidemiologists/clinicians from the beginning (to assure relevance to the application) as well as the technologists (to ensure that the best state-of-the-art solutions are appropriately exploited).

It was concluded that if we wish to make genuine clinical gains and translation, clinicians and biomedical researchers need to be involved in training programmes for technologists. Such interactions are critical to help technologists understand what types of clinical questions would benefit from metabolomics. The more the technologists understand the clinical need to include the types of samples that can be used, their robust collection, analyses, integration with other clinical parameters and linkage to measurable and clinically relevant outcomes, the better the quality and direction of future clinical metabolomics research. Furthermore, technologists would benefit from learning specific examples whereby novel tests have been used to try to improve risk prediction in different disease areas and how the results are judged against the best current predictive algorithms. The relevance of experimental power and replication should also be considered. It was also identified that there is a need to train clinicians to better understand what metabolomics data look like and the complexities of analyses of untargeted data. Thus, better training could help to avoid both underpowered experimental designs and minimising false positives as well as unrealistic clinical expectations.

The Scientific Programme Committee Members are currently preparing a summary publication of the Retreat.

Prof Zhengming Chen (University of Oxford) and Prof George Davey Smith (University of Bristol) apparently happy for their metabolic phenotyping plans.
9.10.2016
Prof Ala-Korpela’s blog on Metabolic Phenotyping in Epidemiology

Metabolic phenotyping, nowadays most often termed metabolomics, is becoming increasingly applied in molecular epidemiology. Recent technological developments resulting in increased numbers of quantitative molecular applications of metabolomics triggered the idea for a themed issue of the IJEon Metabolic Phenotyping in Epidemiology edited by George Davey Smith and Mika Ala-Korpela.

These developments have been driven by mass spectrometry and nuclear magnetic resonance spectroscopy as the two key experimental methodologies that currently allow for studies at an epidemiological scale. The pivotal role of absolute quantification of identified molecular entities in epidemiology and genetics is evident from a multitude of recent applications. The scientific evidence suggests that these kinds of new technologies will aid molecular understanding of metabolic health and diseases. The focus of the themed issue is on the applications of quantitative metabolic phenotyping.

The themed issue will be published in Volume 45, Issue 5 of the IJE. Here we share some of the contributions to the issue, already published on advance access online: https://ije-blog.com/2016/10/09/metabolic-phenotyping-in-epidemiology/.

3.10.2016
Dr Würtz is giving 3 talks in the UK

Comprehensive metabolic profiling has recently become feasible in large cohorts and clinical trials via high-throughput NMR metabolomics. This method quantifies numerous routine and novel blood biomarkers in one go, including lipoprotein subclasses, fatty acids, and amino acids. The high-throughput biomarker profiling is ideally suited for Mendelian randomization and the experimentation is already available at University of Bristol.

The seminars will cover applications of metabolomics to assess cardiovascular event risk, molecular effects of risk factors such as alcohol and adiposity, as well as detailed metabolic signatures of statins and other lipid-lowering drugs. Steps towards clinical translation will be outlined.


12 Oct 2016:
Dr Würtz is giving a talk Metabolomics in Large-Scale Epidemiology — Molecular Signatures of Risk Factors and Drug Interventions on Wednesday 12th October 2016 11:30 - 12:30 in OS6 (Oakfield house) in Bristol, UK.
University of Bristol

17 Oct 2016:
Dr Würtz is giving a talk Metabolomics in Large-Scale Epidemiology — New Biomarkers and Old Drug Targets at UCL Institute of Cardiovascular Science on Monday 17th October 12:30 - 13:30.
Program for UCL seminar (PDF)
UCL Institute of Cardiovascular Science

20 Oct 2016:
Dr Würtz is giving a talk Metabolomics in Large-Scale Epidemiology — Molecular Signatures of Risk Factors and Drug Interventions at University of Cambridge, Department of Public Health and Primary Care on Thursday 20th October 11:00.
Department of Public Health and Primary Care

17.8.2016 Article in International Journal of Epidemiology
Press release: Molecular research on alcohol effects questions benefits of moderate drinking

Modest alcohol drinking is commonly considered beneficial for heart health. Scientifically, the issue is however still controversial. A new study found that alcohol consumption was associated with a complex metabolic profile in blood, comprising some favourable effects but mostly adverse consequences in relation to heart disease risk. The double-edged effects of alcohol now make it a bit more difficult to justify having that drink for health.

Alcohol is a leading risk factor for death and disability, yet for heart disease many studies have indicated a protective role of moderate drinking. The new research lead by University of Oulu, Finland, examined the relation of alcohol drinking with multiple blood biomarkers among almost 10,000 healthy young Finns. Alcohol consumption was found to be associated with a complex metabolic profile in the blood, covering both some potentially favourable effects but also many adverse effects in relation to the risk of cardiovascular disease. Among the novel effects uncovered were unfavourable changes in the blood concentrations of unsaturated fatty acids and also some amino acids that relate to the risk of heart disease and diabetes.

“These new results provide important information on the complex metabolic effects of alcohol in the general population. The findings are in line with increasing evidence that call into question the protective effects of moderate alcohol consumption on heart health” says Dr. Peter Würtz, lead author of the study from the University of Oulu, Finland.

The metabolic associations with alcohol consumption were found to be similar in 3 different study settings. Further, 1466 study participants were re-examined for alcohol consumption and blood screening 6 years after the initial survey. The metabolic changes among people reporting changes in alcohol drinking were similar to the main findings. These results give confidence that the observed metabolic changes were due to alcohol consumption as such rather than other lifestyle factors clustering among people with higher alcohol consumption. Overall, the molecular effects uncovered help in understanding how alcohol is affecting metabolic health.

The study was led by the Computational Medicine Research Team at the University of Oulu, Finland, and was conducted in collaboration with researchers from, for example, the University of Eastern Finland, the University of Turku, the Finnish National Institute for Health and Welfare, and London School of Hygiene & Tropical Medicine.

The study was published in the International Journal of Epidemiology, a leading epidemiology journal published by Oxford University Press. The publication is freely available at ije.oxfordjournals.org/content/early/2016/08/02/ije.dyw175.long.

P Würtz, S Cook, Q Wang, M Tiainen, T Tynkkynen, AJ Kangas, P Soininen, J Laitinen, J Viikari, M Kähönen, T Lehtimäki, M Perola,S Blankenberg, T Zeller, S Männistö, V Salomaa, M-R Järvelin, OT Raitakari, M Ala-Korpela, DA Leon Metabolic profiling of alcohol consumption in 9778 young adults International Journal of Epidemiology 45, 1493-1506, 2016

1.8.2016
Dr Würtz is giving a talk

Dr Würtz is giving a talk entitled Metabolomic profiling of statin therapy: longitudinal evidence and Mendelian randomization at the European Lipoprotein Club Meeting in Tutzing, Germany, September 5-8, 2016.

European Lipoprotein Club Meeting 2016

1.8.2016
Dr Würtz is giving a talk

Dr Würtz is giving a talk entitled Metabolomic profiling of statin therapy: Mendelian randomization and longitudinal evidence at the European Society of Cardiology Congress in Rome, Italy on Aug 29, 2016 and present a poster on Comprehensive metabolic profiling of alcohol consumption in 9778 young adults on Aug 30, 2016.

Programme

12.8.2016
Prof Ala-Korpela is giving a talk

Prof Ala-Korpela is giving a talk at the Minerva Institute for Medical Research, Biomedicum (at 12 noon - BM1, 5. floor), Helsinki, on 12th August. His talk is entitled Quantitative serum metabolomics in large-scale systems epidemiology.

Minerva Foundation Institute for Medical Research

20.6.2016
Drs Kettunen & Würtz awarded 3-y Academy of Finland Research Grants 330k€ each

Dr Johannes Kettunen and Dr Peter Würtz were recently awarded 5-year Academy of Finland Research Fellow posts for the period of 1.9.2016 - 31.8.2021. These Research Grants are earmark funding to carry out the presented research plans.

14.6.2016 Letter in PNAS
Dr Mäkinen & Prof Ala-Korpela published a letter in PNAS: Metabolomics of aging requires large-scale longitudinal studies with replication

In relation to a recent paper published in PNAS (Chaleckis R et al. (2016) Individual variability in human blood metabolites identifies age-related differences. Proc Natl Acad Sci USA 113:4252­4259), Dr Mäkinen & Prof Ala-Korpela discuss the importance of (i) metabolic heterogeneity of individuals, (ii) cross-sectional vs. longitudinal study design, (iii) multiple statistical tests, and (iv) independent biological replication. Please see the reply of some of the authors of the original article to evaluate if the message in the letter got understood.

V-P Mäkinen, M Ala-Korpela Metabolomics of aging requires large-scale longitudinal studies with replication (Letter to R. Chaleckis et al. PNAS 113, 4252–4259, 2016) PNAS - Proceedings of the National Academy of Sciences of the United States of America 113, E3470, 2016

25.5.2016
Two 5-year Academy of Finland Research Fellow positions to the Computational Medicine Research Team

Dr Johannes Kettunen and Dr Peter Würtz were awarded 5-year Academy of Finland Research Fellow posts for the period of 1.9.2016 - 31.8.2021. Dr Würtz has been in the Computational Medicine Research Team since 2009 when he started as a post-doctoral scientist. He is currently a Docent in Epidemiology (University of Helsinki) and the Head of Molecular Epidemiology in the Team. Dr Kettunen is an Academy of Finland Postdoctoral Researcher, a Docent in Genetics (University of Helsinki) and the Head of Genetics in the Team. He was recruited to the Team from the Institute for Molecular Medicine Finland (FIMM) early 2014.

The work of Dr Kettunen will focus on elucidating molecular mechanisms behind strong systemic biomarkers of all-cause mortality and assessing their possible clinical utility in high-risk patient groups. Dr Würtz will focus on cardiometabolic diseases and achieving better molecular understanding of the underlying risk factors. His ultimate aim is to improve prevention and potentially identify new options for treatment. Both research projects rely strongly on the quantitative high-throughput serum metabolomics platform developed in the Computational Medicine Research Team and the large-scale population data acquired with it.

The Team warmly congratulates Peter & Johannes for their great achievement!

9.5.2016
Prof Ala-Korpela is giving an invited talk

Prof Ala-Korpela is giving an invited talk at the Cardiff University , School of Medicine, on 9th May. His talk is entitled Quantitative serum metabolomics in large-scale epidemiology –­ A cost-effective base towards systems medicine. He will also be meeting Faculty Members at the Systems Immunity University Research Institute.

22.4.2016 Article in Scientific Reports
Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

This study was led by Dr Tarja Porkka-Heiskanen (Stenberg) from The Sleep Team Helsinki, University of Helsinki, Finland. The Sleep Team is studying the impact of sleep loss on immune defence and metabolism, particularly on lipid and cholesterol metabolism.

Prof Mika Ala-Korpela from the Computational Medicine Research Team was responsible for some population-based aspects of the study and led those systemic metabolic profiling analyses that were based on serum NMR metabolomics.

It has previously been established in epidemiological studies that people who sleep less than they should have a higher risk of cardiovascular diseases, which are known to be linked to both lipid metabolism and the immune system. Sleep loss has been demonstrated to cause a low-grade inflammatory state, which may contribute to the increased risk of cardiovascular diseases. Carbohydrate metabolism has also been found to be altered in sleep deficiency in ways that resemble type 2 diabetes. However, limited information is available on the potential impact of sleep loss on lipid and cholesterol metabolism.

Selected parts from the press release from the University of Helsinki:

Sleep loss detrimental to blood vessels

Getting too little sleep causes changes in the metabolism of cholesterol, demonstrates a study conducted at the University of Helsinki. According to the results, long-term sleep loss may contribute to the development of cardiovascular disease.

Lack of sleep has previously been found to impact the activation of the immune system, inflammation, carbohydrate metabolism and the hormones that regulate appetite. Now University of Helsinki researchers have found that sleep loss also influences cholesterol metabolism.

The study examined the impact of cumulative sleep deprivation on cholesterol metabolism in terms of both gene expression and blood lipoprotein levels. With state-of-the-art methods, a small blood sample can simultaneously yield information about the activation of all genes as well as the amounts of hundreds of different metabolites. This means it is possible to seek new regulating factors and metabolic pathways which participate in a particular function of the body.

In this case, we examined what changes sleep loss caused to the functions of the body and which of these changes could be partially responsible for the elevated risk for illness, explains Vilma Aho, researcher from the Sleep Team Helsinki research group.

The study established that the genes which participate in the regulation of cholesterol transport are less active in persons suffering from sleep loss than with those getting sufficient sleep. This was found both in the laboratory-induced sleep loss experiment and on the population level.

While analysing the different metabolites, the researchers found that in the population-level data, persons suffering from sleep loss had fewer high-density HDL lipoproteins, commonly known as the good cholesterol transport proteins, than persons who slept sufficiently.

Together with other risk factors, these results help explain the higher risk of cardiovascular disease observed in sleep-deprived people and help understand the mechanisms through which lack of sleep increases this risk.

It is particularly interesting that these factors contributing to the onset of atherosclerosis, that is to say, inflammatory reactions and changes to cholesterol metabolism, were found both in the experimental study and in the epidemiological data, Aho says.

The results highlight the health impact of good sleep. The researchers emphasise that health education should focus on the significance of good, sufficient sleep in preventing common diseases, in addition to healthy food and exercise. Even a small reduction in illnesses, or even postponing the onset of an illness, would result in significant cost savings for society at large.

The experimental study proved that just one week of insufficient sleep begins to change the body’s immune response and metabolism. Our next goal is to determine how minor the sleep deficiency can be while still causing such changes, Aho states.

V Aho, HM Ollila, E Kronholm, I Bondia-Pons, P Soininen, AJ Kangas, M Hilvo, I Seppälä, J Kettunen, M Oikonen, E Raitoharju, T Hyötyläinen, M Kähönen, JSA Viikari, M Härmä, M Sallinen, VM Olkkonen, H Alenius, M Jauhiainen, T Paunio, T Lehtimäki, V Salomaa, M Orešič, OT Raitakari, M Ala-Korpela, T Porkka-Heiskanen Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses Scientific Reports 6, 24828, 2016

4.4.2016
Dr Würtz is giving a talk

Dr Würtz is giving a talk entitled Comprehensive metabolic profiling of statin therapy: longitudinal evidence and Mendelian randomization at the Scandinavian Atherosclerosis Conference in Copenhagen, Denmark (14 April 2016).

The website of the conference & Programme

23.3.2016 Article in Nature Communications
Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

An understanding of the genetic factors involved in systemic metabolism and their associations with chronic disease is a key objective. Metabolic phenotypes serve as good intermediate traits for a genome-wide association study (GWAS) and blood metabolites can be potentially used to discover genetic determinants of circulating metabolites, and particularly to understand the metabolic context of disease-associated genetic variants.

In this study, detailed molecular profiles of circulating metabolites were analysed for almost 25,000 individuals to increase knowledge on genetic regulation of systemic metabolism. Our main findings were twofold. Firstly, a discovery of 8 new genetic loci for circulating metabolites and fatty acids. The new associated loci contained either transporters or enzymes closely involved in the metabolism or trafficking of the associated metabolite. These new data are now available to be used to study the potential causality of a plethora of biomarkers and to better understand the intricate metabolic effects of known risk factors. Secondly, in our search for new metabolic pathways in relation to known disease associated variants, we found that a known CHD associated variant near LPA was linked with circulating triglycerides and VLDL metabolism. Due to these new metabolic findings for this particular variant, we focused on this region and fine mapped the genetic architecture of Lp(a). In fact, we were able to generate a gene score that explained over 45% of the variation in Lp(a) in the replication cohort. The metabolic associations were strengthened with the stronger genetic instrument. Subsequently, we used the genetic risk score in Mendelian randomization to show that the discovered novel effects of Lp(a) synthesis on overall lipoprotein and triglyceride metabolism are causal. Furthermore, as we now had a strong genetic risk score for Lp(a), we could use it for reverse genetics in combination with electronic health records. Intriguingly, according to extensive electronic health record data, the genetic variation in LPA appears to be associated with ischemic heart disease but not with other common adverse disease events. Thus, our results provide the first evidence of the potential consequences to lipoprotein metabolism when people are treated with emerging drugs (a phase 2 trial for LPA mRNA antisense oligonucleotides is currently active). Our findings also provide support that the treatment may well be suitable for CHD risk reduction and is likely to be free of other strong morbidities. This study also serves as a proof of concept in terms of how large multiomics biobank data could be efficiently used to inform drug discovery at an early stage.

Press release (PDF)

J Kettunen, A Demirkan, P Würtz, HHM Draisma, T Haller, R Rawal, A Vaarhorst, AJ Kangas, LP Lyytikäinen, M Pirinen, R Pool, AP Sarin, P Soininen, T Tukiainen, Q Wang, M Tiainen, T Tynkkynen, N Amin, T Zeller, M Beekman, J Deelen, KW van Dijk, JJ Hottenga,EM van Leeuwen, T Lehtimäki, E Mihailov, RJ Rose, AJM de Craen, C Gieger, M Kähönen, M Perola, Blankenberg S, Savolainen MJ, Verhoeven A, Viikari J, Willemsen G, Boomsma DI, van Duijn CM, Eriksson J, Jula A, Järvelin MR, Kaprio J, Metspalu A, Raitakari O, Salomaa V, PE Slagboom, M Waldenberger, S Ripatti, M Ala-Korpela Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA Nature Communications 7, 11122, 2016

23.3.2016 Article in Nature Communications
Uuden lääkeaineen turvallisuutta voidaan selvittää geenitiedon avulla

Suomalaisvetoinen kansainvälinen tutkijaryhmä on onnistunut kartoittamaan kehitteillä olevan uuden sydäntautilääkkeen taustoja. He havaitsivat, että tulevalla lääkityksellä ei todennäköisesti ole voimakkaita sivuvaikutuksia. Havainto oli mahdollinen genetiikan ja laajojen elektronisten potilastietojen avulla. Uusi lääkityksen kohde on LPA-geeni. Tutkimustulokset antavat alustavaa varmistusta siitä, että tuleva lääkeaine on turvallinen käyttää ja auttaa alentamaan sydäntautiriskiä muiden markkinoilla olevien sydäntautilääkkeiden lisäksi.

Tutkijoiden aineenvaihdunnan perintötekijöitä kartoittanut laaja tutkimus johdatti heidät LPA-geenin jäljille, kun he huomasivat, että LPA-geeni muokkaa koehenkilöiden rasva-aineenvaihduntaa aiemmin tuntemattomalla tavalla. Tutkiakseen tarkemmin tätä havaintoa he kartoittivat LPA-geeniin liittyvät perintötekijät erittäin tarkasti. Näitä perintötekijöitä hyödyntämällä he pystyivät tutkimaan kehitteillä olevan lääkkeen mahdollisia sivuvaikutuksia.

He havaitsivat laajassa elektronisessa potilastietoarkistossa, että LPA-geenin perintötekijät liittyivät ainoastaan sydäntautiriskiin, mutta eivät mahdollisiin voimakkaisiin sivuvaikutuksiin. Tällainen geeni- ja aineenvaihduntatietoa ja laajoja elektronisia tietoaineistoja yhdistävä tutkimus on uusi voimakkaasti maailmalla nouseva tutkimusalue, jolla uskotaan olevan merkittävä rooli esimerkiksi lääkeaineiden kehityksen nopeuttamisessa ja kustannusten alentamisessa.

”Tämä tutkimus on merkittävä avaus siinä suhteessa, että pystyimme geenitietoa käyttämällä alustavasti arvioimaan tulevan lääkeaineen mahdollisia sivuvaikutuksia”, sanoo dosentti Johannes Kettunen, yksi tutkimuksen johtajista, Oulun yliopistosta. ”Luonnollisesti lääketutkimukset täytyy viedä loppuun, jotta tulevan lääkkeen riskeistä ja hyödystä saadaan varmuus ja tarkempaa tietoa, mutta nämä löydökset ovat jo sinällään lupaavia; tällainen lähestymistapa tullee myös muuttamaan lääketutkimuksen toimintaperiaatteita tulevaisuudessa”, Kettunen jatkaa.

Tutkimuksessa käytettiin yli 37 000 eurooppalaisen vapaaehtoisen tutkittavan näytteitä, ja aineenvaihduntatuotteita kartoitettiin Oulun ja Itä-Suomen yliopistojen yhteistyössä kehitetyllä uudella verianalyysillä. LPA-geenin tuottama proteiini muodostaa veressä kulkevan lipoproteiini(a):n, joka on kolesterolista riippumaton sydäntaudin riskitekijä. Osalla väestöstä on perintötekijöistä johtuen korkeat lipoproteiini(a)-tasot ja erityisesti heille tulevasta lääkeaineesta uskotaan olevan erityistä hyötyä.

Tutkimus tehtiin laajassa kansainvälisessä yhteistyössä, eivätkä tutkijat ole yhteydessä lääkekehitystä tekevään yritykseen. Tutkimukseen osallistuivat Oulun yliopiston laskennallisen lääketieteen tutkimusryhmän lisäksi Suomesta mm. Helsingin, Turun, Tampereen ja Itä-Suomen yliopistot sekä Terveyden ja hyvinvoinnin laitos ja ulkomailta mm. Bristolin ja Leidenin yliopistot ja Viron genomikeskus.

J Kettunen, A Demirkan, P Würtz, HHM Draisma, T Haller, R Rawal, A Vaarhorst, AJ Kangas, LP Lyytikäinen, M Pirinen, R Pool, AP Sarin, P Soininen, T Tukiainen, Q Wang, M Tiainen, T Tynkkynen, N Amin, T Zeller, M Beekman, J Deelen, KW van Dijk, JJ Hottenga,EM van Leeuwen, T Lehtimäki, E Mihailov, RJ Rose, AJM de Craen, C Gieger, M Kähönen, M Perola, Blankenberg S, Savolainen MJ, Verhoeven A, Viikari J, Willemsen G, Boomsma DI, van Duijn CM, Eriksson J, Jula A, Järvelin MR, Kaprio J, Metspalu A, Raitakari O, Salomaa V, PE Slagboom, M Waldenberger, S Ripatti, M Ala-Korpela Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA Nature Communications 7, 11122, 2016

22.3.2016
Prof Prof Ala-Korpela invited to attend the BBMRI-ERIC “2nd-B” Workshop on Biomolecular resources in Uppsala Sweden on 12-13 April, 2016

Excellence in biobank research depends on integration of outstanding sample collections, profound medical insights, and advanced analytic technologies. The first “B” of BBMRI-ERIC, Biobanks, has set in motion several objectives towards operational and sustainable e-infrastructure for biobanks. Over 500 biobanks with more than 60 million samples are currently hosted in the Directory of BBMRI-ERIC, which provides contacts and communication between the biobanks and investigators for identification of samples and data types of interest. With this workshop, the second “B” of BBMRI­-ERIC, Biomolecular resources, shall be addressed. The goal is to draft a roadmap for the BBMRI-ERIC Biomolecular resources, whether through establishing a Common Service for Biomolecular resources or other feasible means.

19.3.2016
Talk by Dr Würtz

Dr Würtz is giving a talk entitled Comprenehsive metabolic profiling of statin therapy: longitudinal evidence and Mendialin randomization at the Finnish Atherosclerosis Society Annual Meeting in Helsinki, Finland (18-19 March 2016).

Program (PDF)

18.3.2016
Sigrid Jusélius Foundation continues to fund Computational Medicine Research Team

Prof Ala-Korpela, as the Head of the Computational Medicine Research Team, was awarded a 2-year research grant from the Sigrid Jusélius Foundation for the research entitled Population-based stratification of individual cardiovascular risk — a multi-omics approach; the grant will be 100,800 € for the period of two years (1.5.2016-30.4.2018).

All the given grants can be found here. (PDF)

Selected summary from the grant application (28 Nov 2015) regarding the research achievements in the team over the last 2 years:

The Team has taken systemic metabolic phenotyping to unprecedented numbers and illustrated the great potential of multi-omics research in the molecular understanding of common metabolic diseases. The fully automated NMR metabolomics platform for comprehensive lipoprotein, lipid and metabolite quantification of human serum and plasma, developed in the Team during the last 10 years, has now been applied to profile over 350,000 samples. This platform provides quantitative molecular data on ~250 metabolic measures. Utilising these extensive systemic metabolic data from multiple population-based cohorts, we have made novel biomarker findings in relation to ageing (Nature Comm 2014; n>20,000) and to the short-term risk of all-cause mortality (PLoS Med 2014; n=17,345). We have also indicated remarkable genetic pleiotropy in relation to lipoprotein metabolism (JACC 2013; n=10,547) and made an extensive study with Mendelian randomization to estimate causal effects of BMI on systemic metabolism across multiple metabolic pathways (PLoS Med 2014; n=12,664). In addition, we have led a proof-of-principle study on NMR-based molecular profiling of CVD biomarkers and risk in three large prospective cohorts of 13,500 individuals with 1,740 incident events; this represents the largest metabolomics study on CVD to date (Circulation 2015) and substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment in CVD. Together with our world-leading epidemiology colleagues and the largest biobanks in the world, we are in an excellent position to provide novel insights into the value of personal metabolic phenotypes in CVD risk assessment. As a recognition of our key contributions in multi-omics systems epidemiology, Prof Ala-Korpela was invited to contribute to a position paper on circulating biomarkers in atherosclerotic vascular disease (EHJ 2015).

Selected summary from the grant application (28 Nov 2015) regarding the medical importance of the suggested research:

Notable advances have taken place in the understanding and treatment of cardiovascular diseases (CVD). However, it remains the leading cause of morbidity and mortality in Finland and worldwide. Risk assessment at early stages, where the disease is still reversible, would allow targeted primary prevention. Identification of those individuals that would benefit from life-style decisions or preventive medication is the key for cost-effective health care to prevent disease development and the associated societal cost burden. However, established risk factors – dyslipidaemia, smoking, hypertension and diabetes – often fail to identify those who will eventually develop CVD. The work suggested here aims to improve individual cardiovascular risk assessment by conducting high-throughput NMR-based metabolomics profiling of serum samples in extensive population cohorts at unprecedented sample-sizes. The population-scale of the project allows us to go beyond biomarker discovery. The key aim is to evaluate risk models for cardiovascular disease in various metabolic strata, e.g., men and women, obese individuals, people with low LDL cholesterol or in people grouped on the basis of their comprehensive systemic metabolic profile. We anticipate that the biomarkers and risk models for the clinical outcome differ for people based on their metabolic status as well as they differ for specific CVD outcomes, e.g., heart attack or stroke. Our recent publications and preliminary findings strongly support these hypotheses. The novel high-throughput serum NMR metabolomics platform, developed in the Team, enables cost-effective production of individual systemic metabolic profiles with around 250 measures – the only existing methodology applicable in large-scale epidemiology. This research will include pioneering numbers of individuals: ~300,000 in the beginning of the project and towards a million by the end of it. The suggested novel work is supported by international leaders in the field of cardiovascular science via collaboration and data from population-based epidemiological cohorts and clinical trials. This is an exceptional international endeavour of high scientific and societal importance.

11.3.2016
Invited talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk at the China Kadoorie Biobank Meeting in Oxford on 11th March.

The China Kadoorie Biobank Annual Research Day is held on 11 March at the University of Oxford. Prof Ala-Korpela's invited talk is introducing quantitative serum NMR metabolomics together with some pilot results and the fascinating prospects of metabolomics applications in the CKB.

Program (PDF)

7.3.2016 Article in the Journal of the American College of Cardiology
Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase

HMG-CoA reductase (HMGCR) inhibitors, commonly known as statins, reduce low-density-lipoprotein cholesterol (LDL-C) levels leading to proportionate reduction in cardiovascular risk. Statins have become first-line therapy for cardiovascular prevention, making them the most widely prescribed drug class worldwide. However, their systemic effects across lipoprotein subclasses, fatty acids and circulating metabolites remain incompletely characterized. In this work we determined comprehensive metabolic effects of statin therapy by conducting metabolomic profiling at two time-points in four population-based cohorts. To verify that the observed lipoprotein, fatty acid and metabolic changes were due to the effects of statins, the results were corroborated via Mendelian randomization by using a genetic variant in the HMGCR gene as a proxy for the pharmacological action of statins.

Metabolic profiling of statin use in longitudinal cohorts uncovered an intricate association pattern of circulating lipoprotein, fatty acid and metabolite changes, which add to our understanding of the LDL-C independent effects of statins. Statin use was associated with pronounced lowering of numerous lipids and fatty acids consistent with the cardioprotective effects. Interestingly, our results suggest a more efficacious role of statins for lowering remnant cholesterol levels than would be expected based on the ability of statins to lower circulating triglycerides. In contrast, statin use did not markedly affect the circulating levels of recently identified biomarkers for cardiometabolic risk such as amino acids, glycolysis and glycogenesis related metabolites or ketone bodies. The genetic proxy for HMGCR inhibition gave rise to a strikingly similar association pattern, providing unconfounded evidence that the observed metabolic changes arise as a consequence of the mechanism-based effect of statins.

The exquisite match between the metabolic association patterns from observational and genetic analyses serves as a proof-of-concept illustrating how the combination of metabolomics and genetic proxies for drug mechanisms can facilitate the assessment of pharmacological action and on‑target effects for known therapies and novel drug targets. While Mendelian randomization of drug targets has been used previously, this study is the first to combine the concept with observational results across a wide range of cardiometabolic biomarkers. The insights into an extensively studied therapeutic illustrate how metabolomics, combined with genetic proxies mimicking pharmacological action, can elucidate the molecular effects of known targets, clarify treatment indication and potentially be used to inform drug development. As extensive metabolomics and genetic data are becoming increasingly available in large biobanks, we anticipate that comprehensive molecular profiling will prove as a cost-effective solution to augment drug development in both pre-clinical and clinical trial stages.

Press release (PDF)

P Würtz, Q Wang, P Soininen, AJ Kangas, G Fatemifar, T Tynkkynen, M Tiainen, M Perola, T Tillin, AD Hughes, P Mäntyselkä, M Kähönen, T Lehtimäki, N Sattar, AD Hingorani, J-P Casas, V Salomaa, M Kivimäki, M-R Järvelin, G Davey Smith, M Vanhala, DA Lawlor, OT Raitakari, N Chaturvedi, J Kettunen, M Ala-Korpela Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase JACC – Journal of the American College of Cardiology 67, 1200-1210, 2016

Editorial for the paper

In summary, the work by Würtz et al. represents an important proof-of-concept study that observational data can be used to characterize drug responses using pharmacometabolomics by confirming these results with a “natural” clinical trial using Mendelian randomization concepts.

V Deepak, SH Shah Pharmacometabolomics meets genetics : a “natural” clinical trial of statin effects JACC - Journal of the American College of Cardiology 67, 1211-1213, 2016

7.3.2016 Article in the Journal of the American College of Cardiology
Uutta aineenvaihduntatietoa statiinien hyödyistä - laskennallisen lääketieteen ryhmän johtama kansainvälinen tutkimus julkaistiin tänään amerikkalaisessa kardiologian huippulehdessä JACC

Statiinit (veren kolesterolia alentavat lääkkeet) ovat käytössä sadoilla tuhansilla suomalaisilla, mutta silti niiden yksityiskohtaiset vaikutukset aineenvaihduntaan ovat osin selvittämättä. Suomalaistutkijoiden kehittämä uusi verianalyysi auttoi paljastamaan statiinien odottamattomia hyötyjä sekä sulkemaan pois tiettyjä sivuvaikutuksia. Käytetyn tutkimusasetelman ja verianalyysin oletetaan myös jatkossa olevan merkittävä edistysaskel lääkekehityksessä, alentavan sen kustannuksia, lisäävän turvallisuutta ja nopeuttavan uusien lääkkeiden kehittämistä.

Oulun yliopiston tutkijoiden johtamassa kansainvälisessä tutkimuksessa löydettiin statiinien uusia vaikutuksia aineenvaihduntaan. Tutkijat käyttivät Oulun ja Itä-Suomen yliopistojen yhteistyönä kehitettyä uutta verianalyysiä ja geenitietoa lähes 28 000 vapaaehtoiselta tutkittavalta ja osoittivat, että statiinit vaikuttavat aineenvaihduntaan aiemmin tuntemattomalla tavalla. Tulokset auttavat ymmärtämään statiinien monipuolisia positiivisia vaikutuksia sydäntautiriskin alentamisessa. Käytettyä menetelmää voidaan jatkossa hyödyntää myös uusien sydän- ja verisuonitautilääkkeiden aineenvaihduntavaikutusten sekä mahdollisten sivuvaikutusten arvioinnissa.

Uuden verianalyysin avulla pystytään määrittämään muitakin sydäntaudin riskitekijöitä kuin rasva-aineet. Tutkijat havaitsivatkin, että statiineilla ei näyttäisi olevan epäedullista vaikutusta uusiin veren merkkiaineisiin, kuten esimerkiksi eräisiin aminohappoihin, jotka liittyvät sekä riskiin sairastua sydäntauteihin että tyypin 2 diabetekseen. Vaikkakin statiinien tiedetään olevan erittäin turvallisia lääkkeitä, tällainen tarkka aineenvaihdunnallinen tieto on erittäin hyödyllistä ja auttaa myös uusien lääkkeiden kehitystyössä.

Kehitetystä tutkimusasetelmasta on merkittävää hyötyä jatkossa aineenvaihdunnallisten tautien ehkäisemiseen tarkoitettujen uusien lääkkeiden kehityksessä – laajan metabolisen tiedon ja geneettisen tiedon yhdistäminen mahdollistaa lääkkeiden aiheuttamien aineenvaihdunnallisten muutosten tutkimukset jo varhaisessa kehitysvaiheessa, ennen varsinaisten lääkekokeiden aloittamista. Näin kokeiden turvallisuus parantuu ja lääkekehityksen kokonaiskustannukset alentuvat, jopa erittäin merkittävästi, toteaa dosentti Johannes Kettunen, yksi tutkimuksen johtajista Oulun yliopistosta.

Tutkimuksen mahdollisti laskennallisen lääketieteen tutkimusryhmän kehittämä erittäin kustannustehokas uusi verianalyysi. Menetelmällä saadaan määritettyä yhdestä verinäytteestä yli 200 biologista merkkiainetta, jotka kuvaavat monipuolisesti kehon aineenvaihdunnan tilaa. Analyysimenetelmä onkin jo käytössä monissa Eurooppalaisissa biopankeissa ja se on leviämässä maailmanlaajuiseen käyttöön.

Tutkimus tehtiin laajassa kansainvälisessä yhteistyössä Oulun yliopiston laskennallisen lääketieteen tutkimusryhmän johtamana. Siihen osallistuivat mm. Oulun, Turun, Tampereen ja Itä-Suomen yliopistot, Terveyden ja hyvinvoinnin laitos ja Englannista University College London ja Bristolin yliopisto.

P Würtz, Q Wang, P Soininen, AJ Kangas, G Fatemifar, T Tynkkynen, M Tiainen, M Perola, T Tillin, AD Hughes, P Mäntyselkä, M Kähönen, T Lehtimäki, N Sattar, AD Hingorani, J-P Casas, V Salomaa, M Kivimäki, M-R Järvelin, G Davey Smith, M Vanhala, DA Lawlor, OT Raitakari, N Chaturvedi, J Kettunen, M Ala-Korpela Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase JACC – Journal of the American College of Cardiology 67, 1200-1210, 2016

18.1.2016
Keynote lecture by Dr Kettunen

Dr Kettunen is giving a keynote lecture in the Rantakallio symposium on 15th - 17th June 2016.

Dr Kettunen is giving a talk entitled Molecular mechanisms behind disease biomarkers - a systems medicine approach in the Rantakallio symposium in June. The conference is dedicated to the memory on Professor Paula Rantakallio who started the research of children born in 1966 in Northern Finland (Northern Finland Birth Cohort 1966, NFBC 1966). The work started during early pregnancy and is still ongoing with the study subjects having reached 48 years of age. In 1980’s a new birth cohort study (NFBC 1986) was initiated for children born in 1985-1986.

Website of Conference on Epidemiological Birth Cohort Studies 2nd Paula Rantakallio symposium & 6th Conference on Epidemiological Longitudinal Studies in Europe, CELSE

18.12.2015
Talk by Dr Kettunen

Docent Kettunen gives a talk at the The 13th International Congress of Human Genetics in April 2016, Kyoto, Japan

The ICHG2016 meeting will be the first to be held in Asia in its history, hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) in conjunction with the Japan Society of Human Genetics. Recent spectacular advancement in the technologies of genome analyses including next generation sequencing and in the informatics of huge data including genome sequences and medical information, are bringing exceptional opportunities for better understanding our human genome and diseases, and, furthermore, for developing more efficacious treatment for diseases. ICHG2016 will be an exciting opportunity to share latest development in human genetics and discuss the future of human genetics.

The 13th International Congress of Human Genetics

2015

15.12.2015
Scientific collaboration meeting with Prof Perola Group (THL) and the Estonian Genome Center (University of Tartu)

The meeting takes place in Vierumäki 15th – 16th December 2015 and is organised by Prof Perola Group. From the Computational Medicine Research Team the following presentation are given:

Prof Mika Ala-Korpela
The present and the future of serum NMR metabolomics in large-scale systems epidemiology

Dr Johannes Kettunen
Genetics and intermediate traits to unravel molecular pathways leading to complex diseases

Dr Peter Würtz
Metabolic profiling of drug effects: statins and beyond

Qin Wang
Sex hormone-binding globulin: observational and causal effect estimates on lipids, metabolites and type 2 diabetes

1.12.2015
A docentship in Epidemiological Metabolomics appointed to Dr Pasi Soininen at the University of Oulu, Finland

Dr Pasi Soininen is an Assistant Professor of Pharmaceutical Chemistry at the School of Pharmacy, University of Eastern Finland (Kuopio Campus) & the Head of the NMR Metabolomics Laboratories at the UEF as well as at the University of Oulu. He is an internationally renowned expert in experimental NMR spectroscopy and in quantitative spectral analysis. He has over 15 years of experience in chemical and biological applications of quantitative proton NMR spectroscopy. Dr Soininen's research interests are in the development of high-throughput quantitative NMR metabolic profiling methodologies for various biofluids and their translation into biological and medical research. He has published over 100 articles in international peer-reviewed journals.

-The recent 10 years in the area of quantitative metabolomics have been thrilling. It is now evident that our long-term choice to focus only on quantitative targeted high-throughput metabolomics has been spot on. At the moment our serum NMR metabolomics platform is leading the scene in epidemiological metabolomics and is the only possible one for cost-effective quantitative analyses of large-scale studies and extensive biobanks, Pasi comments.

More information on the abovementioned platform can be found in a recent publication:

P Soininen, AJ Kangas, P Würtz, T Suna, M Ala-Korpela Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics Circulation: Cardiovascular Genetics 8, 192-206, 2015

A biography of Docent Soininen can be found here.

The Computational Medicine Research Team congratulates Pasi for this great achievement!

23.11.2015
Talk by Dr Würtz

Dr Würtz is giving a talk entitled High-throughput NMR metabolomics at the cost of routine clinical chemistry at Kuopio University Hospital (Department of Clinical Chemistry) on 9th December 2015 at 14:15-15:15.

Integration of complementary omics platforms allows unprecedented biological details across multiple molecular pathways and is leading to a conceptual shift in disease risk assessment from individual biomarkers to multi-marker profiles. Ultimately, the application and value of new biomarkers and profiles will depend on their predictive power over traditional risk assessment, on their reproducibility in multiple cohorts and on the practicalities and the cost-effectiveness of their integration into clinical routines and laboratories. Our quantitative high-throughput serum NMR metabolomics platform is on its way to be incorporated as a routine methodology in large-scale epidemiology and biobanks; this makes perfect sense both from the biological research and cost point of view ­ the extensive molecular data vastly extend the relevance of the sample collections and make many separate clinical chemistry assays redundant. The current scientific evidence already lends support to conclude that this can lead to both better assessment of individual disease risks and savings in research as well as in health care expenditure along with successful clinical translation.

Website of ISLAB (in Finnish)

16.11.2015
Dosentti Kettunen ja laskennallinen lääketiede YLE:n Akuutti-ohjelmassa

Dosentti Johannes Kettunen kertoo uusista tutkimustuloksista ja kroonisesta tulehduksesta YLE:n Akuutissa maanantaina 16.11. klo 18:30, jonka jälkeen ohjelma löytyy myös YLE:n Areenasta.

Ohjelma on 16.12.2015 saakka katsottavissa täältä

13.11.2015
Prof Ala-Korpela is giving a talk at the Biocenter Oulu and Biocenter Kuopio minisymposium at the University of Eastern Finland on 13th November 2015

The Computational Medicine Team has been selected as part of Biocenter Oulu for the period 2016-2019. The annual minisymposium of Biocenter Oulu and Biocenter Kuopio is this year focusing on protein and metabolite research.

Prof Ala-Korpela's talk, entitled Quantitative serum metabolomics in large-scale epidemiology ­ A cost-effective base towards systems medicine, will be at 13:20 - 13:35 in the Tietoteknia Auditorium at the University of Eastern Finland.

Program (PDF)

12.11.2015
Prof Ala-Korpela and Dr Würtz are talking at the BBMRI Metabolomics Workshop at the Leiden University Medical Center on 26th January 2016

BBMRI-NL actively promotes collaboration and standardization between biobanks in the Netherlands. In the lead of Prof Eline Slagboom from the Leiden University Medical Centre, the Dutch BBMRI Metabolomics Consortium has taken a forerunner position in applying quantitative serum NMR metabolomics in multiple cohorts hosted by the BBMRI-NL. The workshop on 26-27 January 2016 is the second seminar in succession focusing on metabolomics applications in BBMRI-NL.

Prof Ala-Korpela's talk will focus on analytical and sample quality control issues in serum metabolomics and Dr Würtz will highlight some recent biological novelties in this field from the Computational Medicine Research Team.

BBMRI's Metabolomics workshop

Biobanking and BioMolecular resources Research Infrastructure The Netherlands (BBMRI-NL)

11.11.2015
Talk by Dr Würtz

Dr Würtz is giving a talk entitled High-throughput NMR metabolomics at the cost of routine clinical chemistry at the The Hospital District of Helsinki and Uusimaa Clinical Chemistry Seminar Series at Meilahti Hospital, Helsinki, on 11th November 2015.

Integration of complementary omics platforms allows unprecedented biological details across multiple molecular pathways and is leading to a conceptual shift in disease risk assessment from individual biomarkers to multi-marker profiles. Ultimately, the application and value of new biomarkers and profiles will depend on their predictive power over traditional risk assessment, on their reproducibility in multiple cohorts and on the practicalities and the cost-effectiveness of their integration into clinical routines and laboratories. Our quantitative high-throughput serum NMR metabolomics platform is on its way to be incorporated as a routine methodology in large-scale epidemiology and biobanks; this makes perfect sense both from the biological research and cost point of view ­ the extensive molecular data vastly extend the relevance of the sample collections and make many separate clinical chemistry assays redundant. The current scientific evidence already lends support to conclude that this can lead to both better assessment of individual disease risks and savings in research as well as in health care expenditure along with successful clinical translation.

HUS Medical Meetings

10.11.2015
A four-year doctoral student position available

The position is focused on population-based stratification of individual cardiovascular risk via multi-omics approaches. The position is under main supervision by Johannes Kettunen and is focused on bioinformatics, where multi-omic data are used to understand the molecular mechanisms behind emerging biomarkers and their causal role for cardiovascular disease and other complex traits.

Brief scientific background and rationale for the forthcoming work can be seen here.

Enthusiastic candidates are encouraged to contact Dr Kettunen (johannes.kettunen@computationalmedicine.fi) or Prof Ala-Korpela (mika.ala-korpela@computationalmedicine.fi) for further information.

Please note that the official application must be made according to the instructions and via the link . All the application documents are to be submitted electronically before the deadline on Wednesday 07.12.2015, at 24.00 (midnight, Finnish local time, UTC + 3hr).

9.11.2015
How media saw our work on the metabolic inflammation marker GlycA

Recently published study entitled The biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection, Cell Systems, resounded on the international and internal media. Below a few selected links to the news items.

Science Daily, Science Nordic, Public Broadcasting Service, and Tech Times, among others, wrote articles about the study:
Science Daily: Biomarker for premature death
Science Nordic: Scientists can predict risk of premature death 14 years in advance
Public Broadcasting Service (PBS): Will you die prematurely? This blood test may contain the answer
TechTimes: Blood Test Could Indicate Risks For Premature Death Due To Pneumonia Or Sepsis

In addition, Medical Research.com interviewed Dr Kettunen about the background of the paper and future plans: Chronic Inflammatory Biomarker May Predict Mortality .

Myös suomalaisissa tiedotusvälineissä julkaisu huomioitiin. Muunmuassa Aamulehti kertoi tutkimuksesta jutussaan Suomalaisten läpimurto: Vakavia tauteja voi ennustaa verikokeesta. Sanomalehti Kalevassa aiheesta kerrottiin otsikolla Oululaistutkijat mukana läpimurrossa: vakavia tauteja voi ennustaa verikokeesta ja Iltalehti julkaisi uutisen Verinäyte kertoo riskistä sairastua vakavaan infektiotautiin. Myös Iltasanomat, Mediuutiset ja sanomalehti Karjalainen kertoivat tutkimuksesta.

24.10.2015
Prof Ala-Korpela gave an invited Opening Keynote Speech at the Hong Kong Public Health Forum 2015

The Hong Kong Public Health Forum 2015 on October 24 focused on Extracting Meaning from Data: Cohorts and Deep Analytics. Prof Ala-Korpela's invited Opening Keynote Speech focused on the role of multiple new ‘omics data in epidemiology and public health and how the application of these new analytical technologies can enhance the scientific value of individual population cohorts.




More than 250 colleagues and students including Professor Sophia Chan, Under Secretary for Food and Health, public health practitioners, policymakers and healthcare leaders had attended the Forum, which was a full house event. Please read more and see some more photos and videos at http://sph.hku.hk/phforum2015/photo-highlight .

22.10.2015 Article in Nature Communications
The transcriptional landscape of age in human peripheral blood

Dr Kettunen co-led an article of the transcriptional landscape of age in human peripheral blood that was conducted by a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry. The study identified 1,497 genes that are differentially expressed with chronological age and further showed that CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. The aging-associated transcripts were then used to construct ‘transcriptomic age’ of an individual, and showed that differences between transcriptomic age and chronological age were associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model added biological relevance and complemented existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

MJ Peters, R Joehanes, LC Pilling, C Schurmann, KN Conneely, J Powell, E Reinmaa, GL Sutphin, A Zhernakova, K Schramm, YA Wilson, S Kobes, T Tukiainen, NABEC/UKBEC Consortium, YF Ramos, HHH Göring, M Fornage, Y Liu, SA Gharib, BE Stranger, PL De Jager, A Aviv, D Levy, JM Murabito, PJ Munson, T Huan, A Hofman, AG Uitterlinden, F Rivadeneira, J van Rooij, L Stolk, L Broer, MMPJ Verbiest, M Jhamai, P Arp, A Metspalu, L Tserel, L Milani, NJ Samani, P Peterson, S Kasela, V Codd, A Peters, CK Ward-Caviness, C Herder, M Waldenberger, M Roden, P Singmann, S Zeilinger, T Illig, G Homuth, HJ Grabe, H Völzke, L Steil, T Kocher, A Murray, D Melzer, H Yaghootkar, S Bandinelli, EK Moses, JW Kent, JE Curran, MP Johnson, S Williams-Blangero, H-J Westra, AF McRae, JA Smith, SLR Kardia, I Hovatta, M Perola, S Ripatti, V Salomaa, AK Henders, NG Martin, AK Smith, D Mehta, EB Binder, KM Nylocks, EM Kennedy, T Klengel, J Ding, AM Suchy-Dicey, DA Enquobahrie, J Brody, JI Rotter, Y-D Chen, J Houwing-Duistermaat, M Kloppenburg, PE Slagboom, Q Helmer, W den Hollander, S Bean, T Raj, N Bakhshi, QP Wang, LJ Oyston, BM Psaty, RP Tracy, GW Montgomery, ST Turner, J Blangero, I Meulenbelt, KJ Ressler, J Yang, L Franke, J Kettunen, PM Visscher, GG Neely, R Korstanje, RL Hanson, H Prokisch, L Ferrucci, T Esko, A Teumer, JBJ van Meurs, AD Johnson The transcriptional landscape of age in human peripheral blood Nature Communications 6, 8570, 2015

21.10.2015 Article in Cell Systems
The biomarker GlycA marks chronic inflammation and predicts long-term severe infection risk

This study elucidates GlycA-related molecular and cellular processes by leveraging population-based omics data and health records from >10,000 individuals, including a subset with health records covering nearly 14 years of follow-up. Elevated GlycA levels marked both the acute phase and were chronic within individuals over long periods of time. Gene coexpression network analysis revealed that GlycA was associated with a gene module harbouring a neutrophilic antimicrobial signature. Analysis of infection-related hospitalisation and death records showed that increased GlycA also increased risk of severe non-localised and respiratory infections, particularly septicaemia and pneumonia, independently of C-reactive protein. The results indicate that GlycA is a biomarker for modest chronic inflammation, neutrophil activity, and risk of future severe infections.

This study is an illustration of the utility of leveraging multi-layered omics data and health records to elucidate the molecular and cellular processes associated with biomarkers. As multi-omics studies are becoming increasingly common, biomarker associations with medical histories and health outcomes are likely to improve both patient care and our knowledge on the basic biological mechanisms underlying human disease. This study represents a potentially useful strategy for leveraging omics information for future studies in precision medicine.

Dr Johannes Kettunen from the Computational Medicine Team co-led this work together with Dr Michael Inouye from the Centre for Systems Genomics, School of BioSciences, University of Melbourne, Australia.

SC Ritchie, P Würtz, AP Nath, G Abraham, AS Havulinna, LG Fearnley, A-P Sarin, AJ Kangas, P Soininen, K Aalto, I Seppälä, E Raitoharju, M Salmi, M Maksimow, S Männistö, M Kähönen, M Juonala, S Ripatti, T Lehtimäki, S Jalkanen, M Perola, O Raitakari, V Salomaa, M Ala-Korpela, J Kettunen, M Inouye The biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection Cell Systems 1, 293-301, 2015

30.9.2015
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
Themed Issue on Metabolic Phenotyping in Epidemiology
Special Issue Editor Prof Mika Ala-Korpela
Extended deadline for submissions: 30th September 2015
28.8.2015
Novo Nordisk Foundation funds Computational Medicine

Dr Peter Würtz, Head of Molecular Epidemiology, has been awarded a research grant of 500,000 DKK (~67.000 €) from the Nordic Research Committee of the Novo Nordisk Foundation to support a project entitled "Metabolite Profiling of Insulin Resistance and Type 2 diabetes in Young Adults".

10.8.2015
Prof Ala-Korpela is giving an invited talk at the Big Data Workshop in Oulu on 14th September 2015

Prof Ala-Korpela's talk, entitled The Role of Omics Profiling in Epidemiology, Public Health and Future Medicine, will be at 12:30 - 13:30. The Workshop is in the lecture hall F101 (physiology) at the University of Oulu Medical Campus at 09:15 - 16:00.

5.8.2015
Prof Ala-Korpela is giving an invited talk at The 10th International Conference on Genomics (ICG-10) in Shenzhen, China

The ICG-10 will take place in Shenzhen, China, on October 22-25, 2015. According to the Chairman of the ICG Organizing Committee, Prof. Huanming Yang: "ICG-10 will mark the beginning of a new cycle, as we observe how ‘omics’ research will further transform scientific discoveries into better treatments, and promote better health in the next decade." Prof Ala-Korpela's invited talk is entitled Cost-effective quantitative serum metabolomics in large-scale epidemiology and is in the afternoon on October 25th.

The 10th International Conference of Genomics

9.7.2015
2 four-year doctoral student positions available, starting early 2016

The positions are focused on population-based stratification of individual cardiovascular risk via multi-omics approaches. Brief scientific background and rationale for the forthcoming work can be seen below. One position is focused (more) on the epidemiological and metabolic side of the project (led by Prof Mika Ala-Korpela) and the other (more) on the genetic aspects of the project (led by Dr Johannes Kettunen).

Enthusiastic candidates are encouraged to contact Prof Ala-Korpela (mika.ala-korpela@computationalmedicine.fi) or Dr Kettunen (johannes.kettunen@computationalmedicine.fi) for further information.

Please note that the official application must be made according to the instructions and via http://www.oulu.fi/uniogs/doctoralstudentpositionscall. These positions are under sub-call 9, and all application documents are to be submitted electronically before the deadline on Wednesday 09.09.2015, at 24.00 (midnight, Finnish local time, UTC + 3hr).

1.7.2015
Prof Ala-Korpela puhuu Tieteen päivillä Oulussa 2.9.2015: Mitä verianalyysit kertovat terveydestä ja sairauksista?

Professori Ala-Korpela puhuu Tieteen päivillä keskiviikkona tiedesessiossa Sattumalta terve, osa II, klo 19.10 ­ 20.00. Puheen aiheena on Mitä verianalyysit kertovat terveydestä ja sairauksista? Veren biomarkkereita käytetään lääketieteessä terveyden mittareina ja sairauksien riskien ennustajina. Verensokeri diagnosoi diabeteksen. Diagnoosi perustuu raja-arvoon ja on testihetken tilanne. Kolesteroli ennustaa sydän- ja verisuonitautien kehittymisen riskiä. Sattumalla on kuitenkin tulevaisuuden suhteen merkittävä rooli: vain noin puolella sairastuvista henkilöistä on riskitasolla oleva kolesteroli. Onko mitään tehtävissä sattuman taltuttamiseksi sairauksien riskien arvioinnissa?

Tieteen päivät Oulussa

26.6.2015
Computational Medicine Team selected as part of Biocenter Oulu for the period 2016-2019

Biocenter Oulu is a multidisciplinary umbrella organisation within the Biosciences and Health research focus area of the University of Oulu, Finland. The accepted application from the Computational Medicine Team is entitled Population-based stratification of individual cardiovascular risk ‐ a multi-omics approach and led by Prof Mika Ala-Korpela. Dr Johannes Kettunen is the Vice-Head of the application.

The scientific background and rationale for the forthcoming work

Despite notable advances in the treatment of cardiovascular disease (CVD), it remains the leading cause of morbidity and mortality in Finland and worldwide. The underlying disease progression often remains silent until the clinical manifestations ­ heart attack and stroke ­ occur. Risk assessment at early stages, where the disease is still reversible, would therefore allow an opportunity to target primary prevention. Identification of those individuals that would benefit from individual life-style decisions or preventive medication is the key for cost-effective health care to prevent disease development and the associated societal cost burden. However, established risk factors ­ dyslipidaemia, smoking, hypertension and diabetes ­ often fail to identify who will eventually develop CVD: the majority of first CVD events occurs in people with low or intermediate risk based on current risk prediction scores. Importantly, 50% of people who are hospitalised with heart attacks have normal cholesterol levels.

All people who have suffered from heart disease are recommended statin use; however, the frequency of monitoring, the use of expensive imaging techniques, and aggressiveness of treatment could be guided by novel biomarkers yielding more accurate risk prediction also in these patients. For both primary and secondary CVD prevention, the efficacy of statin treatment differs based on presence of disease, and patient¹s baseline metabolic profile. The variation in response to treatment is wide, but poorly understood. More than 40% of trial patients do not reach target with high-dose statin therapy. There would be a lot of room for improvement since, in general, treatment of approximately 100 people with statins for five years is needed to prevent one heart attack or stroke. A better understanding of the inter-individual response could help to target statin therapy and dose allocation to those patients who would be likely to benefit the most.

Our work aims to improve personalised cardiovascular risk assessment by conducting high-throughput metabolomics profiling of extensive population cohorts as well as drug trials at unprecedented sample-sizes. The population-scale of the project allows us to go beyond biomarker discovery. We anticipate that the biological complexity and heterogeneity of atherosclerotic processes call for individual molecular tailoring of the CVD risk assessment to truly improve the clinical evaluations. We emphasise the need to abandon the current logic of ³one common risk model for all individuals² and to move towards specific molecular identification of people sub-groups. We propose the work detailed here to show that systemic molecular profiling can lead to characterisation of such sub-groups, in the case of which specific risk models will improve CVD risk assessment. The key aim is to evaluate risk models for cardiovascular disease in various metabolic strata, e.g., men and women, obese individuals, people with or without type 2 diabetes, people with low LDL cholesterol, patients with history of vascular disease or individuals grouped on the basis of their comprehensive systemic metabolic profile. We have strong preliminary evidence that the biomarkers and risk models for the vascular outcome differ for people based on their metabolic status as well as they differ for different disease type, e.g., heart attack or stroke. Further, we will test the hypothesis that the detailed baseline metabolic profile can inform on the response to statin therapy ­ as we have shown that it can on the effects of dietary supplements. This would help to identify those who benefit the most from the intervention.

Importantly, in addition to improved risk assessment, the project will provide novel insights into the molecular mechanisms underlying atherosclerosis and thrombosis. The proposed work is a specific extension of our focus on molecular profiling and aetiological understanding of common metabolic diseases. The goals will be achieved by metabolic profiling of multiple extensive population-based cohorts together with several large completed clinical trials using a quantitative serum NMR metabolomics platform developed in the Computational Medicine Research Team. Our work is pioneering in its application of comprehensive systemic metabolic profiling in hundreds of thousands of individuals. The large numbers are a prerequisite for statistically sound metabolic stratifications as well as for understanding the (patho)physiological function of the new disease biomarkers and the causal pathways in disease aetiology with the aid of modern genetic data.

20.6.2015
Prof Ala-Korpela is giving an invited Opening Keynote Speech at the Hong Kong Public Health Forum 2015

The Hong Kong Public Health Forum 2015 on October 24 will focus on Extracting Meaning from Data: Cohorts and Deep Analytics. Prof Ala-Korpela's invited Opening Keynote Speech will focus on the role of multiple new ‘omics data in epidemiology and public health and how the application of these new analytical technologies can enhance the scientific value of individual population cohorts. Quantitative high-throughput serum metabolomics is presented as an example of a new analytical approach to discover potentially important new biomarkers, which could provide better risk stratification both in primary and secondary prevention, and concomitantly lead to better maintenance of individual health and result in overall cost-savings in health care.

In the afternoon (2:30 pm) on October 27th, Prof Ala-Korpela will also give a scientifically focused talk, entitled Quantitative serum metabolomics in large-scale epidemiology – A cost-effective base towards systems medicine, at the Public Health Research Centre at the University of Hong Kong. This talk will discuss cost-effective quantitative serum metabolomics in large-scale systems epidemiology and illustrate the benefits of combining multiple ‘omics data in population-based cohorts. Examples of applying Mendelian randomization analysis to get causal understanding of the metabolic phenomena as well as new applications of comprehensive metabolic phenotyping of drug effects will be presented.

School of Public Health, The University of Hong Kong

28.-29.5.2015
Professor Peter Meikle visiting the Computational Medicine Team in Oulu

Professor Peter Meikle is the Head of the Metabolomics laboratory at Baker IDI Heart and Diabetes Institute in Melbourne, Australia. His laboratory uses state-of-the-art tandem mass spectrometry to obtain lipidomics profiles from cell and animal models in addition to clinically relevant human samples to better characterise the dyslipidemia associated with obesity, diabetes and cardiovascular disease and its relationship to the pathogenesis of these disease states. Professor Meikle and the Computational Medicine Research Team have established scientific collaboration in order to study the interrelationships of data obtained from human serum samples by the mass spectrometry lipidomics techniques applied at Meikle's lab and by the high-throughput serum NMR-metabolomics platform developed in the Computational Medicine Research Team. A particular focus in the collaboration will be on the molecular details of lipoprotein metabolism at subclass level and their potential effects on metabolic disorders.

18.5.2015 Article in Nature Genetics
Dr Kettunen co-authored as a part of the ENGAGE consortium publishes an article of The impact of low-frequency and rare variants on lipid levels

The use of 1000 Genomes imputation reference panel allowed this research to fine map genetic architecture behind known lipid loci, as well as discover new loci for circulating lipids. Additionally, the study was able to highlight several low-frequency coding variants that were most likely the real functional variants behind associated loci.

I Surakka, M Horikoshi, R Mägi, AP Sarin, A Mahajan, V Lagou, L Marullo, T Ferreira, B Miraglio, S Timonen, J Kettunen, M Pirinen, J Karjalainen, G Thorleifsson, S Hägg, JJ Hottenga, A Isaacs, C Ladenvall, M Beekman, T Esko, JS Ried, CP Nelson, C Willenborg, S Gustafsson, HJ Westra, M Blades, AJ de Craen, EJ de Geus, J Deelen, H Grallert, A Hamsten, AS Havulinna, C Hengstenberg, JJ Houwing-Duistermaat, E Hyppönen, LC Karssen, T Lehtimäki, V Lyssenko, PK Magnusson, E Mihailov, M Müller-Nurasyid, JP Mpindi, NL Pedersen, BW Penninx, M Perola, TH Pers, A Peters, J Rung, JH Smit, V Steinthorsdottir, MD Tobin, N Tsernikova, EM van Leeuwen, JS Viikari, SM Willems, G Willemsen, H Schunkert, J Erdmann, NJ Samani, J Kaprio, L Lind, C Gieger, A Metspalu, PE Slagboom, L Groop, CM van Duijn, JG Eriksson, A Jula, V Salomaa, DI Boomsma, C Power, OT Raitakari, E Ingelsson, MR Järvelin, U Thorsteinsdottir, L Franke, E Ikonen, O Kallioniemi, V Pietiäinen, CM Lindgren, K Stefansson, A Palotie, MI McCarthy, AP Morris, I Prokopenko, S Ripatti, ENGAGE Consortium The impact of low-frequency and rare variants on lipid levels Nature Genetics 47, 589-97, 2015

18.5.2015 Article in press in European Heart Journal
Prof Ala-Korpela co-authored a Clinical Review and the European Society of Cardiology (ESC) Working Group of Atherosclerosis and Vascular Biology Position Paper on Novel methodologies for biomarker discovery in atherosclerosis

Identification of subjects at increased risk for cardiovascular events plays a central role in the worldwide efforts to improve prevention, prediction, diagnosis and prognosis of cardiovascular disease and to decrease the related costs. Despite their high predictive value on population level, traditional risk factors fail to accurately predict individual risk. For decades the endeavours to find new biomarkers for prediction, prevention, diagnosis and prognosis of cardiovascular events have focused on a rather small number of molecules. Technological improvements in automated analytical methodologies, for example, in terms of sensitivity and sample throughput, have revolutionized biomarker research in the past ten years. This position paper has a special focus on the emerging -omics technologies, for example the role of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy in the search for new cardiovascular biomarkers. In general, explanatory research related to technical, analytical and practical aspects of new technologies is seen essential and expected to increasingly commence in the near future.

IE Hoefer, S Steffens, M Ala-Korpela, M Bäck, L Badimon, M-L Bochaton-Piallat, CM Boulanger, G Caligiuri, S Dimmeler, J Egido, P C Evans, T Guzik, BR Kwak, U Landmesser, M Mayr, C Monaco, G Pasterkamp, J Tuñón, C Weber Novel methodologies for biomarker discovery in atherosclerosis European Heart Journal 36, 2635-42, 2015

12.5.2015
Interview of Simone Wahl and Harald Grallert on our collaborative work published in BMC Medicine on the multi-omics signature of body weight change

Excess body weight is a major risk factor leading to cardiometabolic diseases. These diseases are among the leading causes of death, therefore heightening the importance of understanding the molecular mechanisms that link the two. Our collaborative research published in BMC Medicine applied a multi-omic approach to study the metabolic consequences of body weight change during a seven year follow up prospective study. Our co-authors Simone Wahl and Harald Grallert from Helmholtz Zentrum München, Germany, explain why it is important to understand the molecular alterations that occur with body weight change,what the key findings were and what the future holds for this research: A link to the interview.

The original article in BMC Medicine
12.5.2015
Invited talk by Dr Würtz

Dr Würtz is giving an invited talk entitled Metabolite profiling & Mendelian randomisation for risk factor characterization and enhanced drug development at the Mendelian Randomization Conference - From Population Health to Pharmaceutical Developments in Bristol, UK (22-24 June 2015).

Mendelian Randomization Conference
Dr Würtz' speaker profile

12.5.2015
Talks by Mrs Wang and Dr Kettunen

Mrs Wang is giving a talk entitled Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates and Dr Kettunen is giving a talk entitled Genome-wide study for blood metabolites identifies 62 loci and links LPA with systemic metabolism at the Mendelian Randomization Conference - From Population Health to Pharmaceutical Developments in Bristol, UK (22-24 June 2015).

Mendelian Randomization Conference

1.5.2015 Article in press in International Journal of Epidemiology
An extensive metabolic profiling and Mendelian randomization analyses on the associations of SHBG with circulating lipids and metabolites and type 2 diabetes

This work reveals important new information regarding the contraversial issue whether circulating sex hormone-binding globulin (SHBG) is causal for type 2 diabetes. In addition, a plethora of new data is disclosed on the relations of SHBG with traditional and new biomarkers of cardiometabolic risk. Circulating SHBG is strongly associated with systemic metabolism and predictive for insulin resistance and diabetes. The weaker causal estimates suggest that the observational associations are partly confounded rather than conferred directly via circulating SHBG.

Q Wang, AJ Kangas, P Soininen, M Tiainen, T Tynkkynen, K Puukka, A Ruokonen, J Viikari, M Kähönen, T Lehtimäki, V Salomaa, M Perola, GD Smith, OT Raitakari, M-R Järvelin, P Würtz, J Kettunen, M Ala-Korpela Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates International Journal of Epidemiology 44, 623-37, 2015

27.4.2015
Key-note Lecture by Prof Ala-Korpela (30 July 2015 - 9:00-10:00 am)

Prof Ala-Korpela is giving an invited Key-note Lecture entitled Metabolomics in precision medicine on 30th July at the HandsOn: Biobanks meeting in Milan, Italy (29-31 July 2015).

HandsOn Biobanks meeting 2015

2.4.2015
Talks by Prof Ala-Korpela (13 June 2015 - 5:00-6:30 pm & 14 June 2015 - 7:45-8:45 am)

Prof Ala-Korpela is giving an invited Plenary talk entitled Metabolite and lipid profiling in cardiovascular risk assessment on 13th June and an invited Breakfast Workshop talk entitled Cost-effective quantitative serum metabolomics in large-scale epidemiology on 14th June at the 25th European Meeting on Hypertension and Cardiovascular Protection in Milan, Italy (12-15 June 2015).

European Meeting on Hypertension and Cardiovascular Protection

24.3.2015
Sigrid Jusélius Foundation funds Computational Medicine

Prof Ala-Korpela, as the Head of the Computational Medicine Research Team, was awarded a 3-year research grant from the Sigrid Jusélius Foundation in 2013 for the research entitled "Life-course metabolic health – population-wide metabolite profiling of cardiometabolic diseases"; the 2015 part of the grant will be 55,800 € for the period of 1.5.2015-30.4.2016.

19.3.2015
Talk by Dr Kettunen (7 June 2015)

Dr Kettunen is giving a talk at the European Conference of Human Genetics in Glasgow, Scotland, UK (6-9 June 2015). The talk is entitled Genome-wide study for metabolic phenotypes identifies 62 loci and elucidates the metabolic context of LPA in coronary heart disease.

European Conference of Human Genetics

16.3.2015
Talks by Dr Würtz (23-26 May 2015)

Dr Würtz is giving two talks at the International Symposium on Atherosclerosis in Amsterdam, The Netherlands (23-26 May 2015). The talks are entitled High-throughput Metabolite Profiling of Cardiovascular Event Risk: A Prospective Study of Three Population-Based Cohorts and Metabolic signatures of adiposity in 12,664 healthy young adults: Causal effects on lipoproteins, fatty acids, inflammation, hormones and amino acids.

International Symposium on Atherosclerosis

21.2.2015 Article published in Circulation: Cardiovascular Genetics
Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Cardiovascular Epidemiology and Genetics

A review-opinion in the growing field of metabolomics in cardiovascular research. Pinpoints the fact that statistically sound epidemiological metabolomics (n > 1,000 people) is yet rare and of about the 30 publications existing, almost 90% are from the authors' team.

P Soininen, AJ Kangas, P Würtz, T Suna, M Ala-Korpela Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics Circulation: Cardiovascular Genetics 8, 192-206, 2015

9.2.2015
Talk by Dr Würtz (14 April 2015)

Dr Würtz is giving a talk entitled Metabolite Profiling and Cardiovascular Event Risk: A Prospective Study of Three Population-Based Cohorts at the Scandinavian Society for Atherosclerosis Research Conference in Copenhagen, Denmark (13-16 April 2015).

Scandinavian Society for Atherosclerosis Research Conference

9.2.2015
Talk by Dr Würtz (24 March 2015 - 11.00-12.30)

Dr Würtz is giving a talk entitled Cost-effective quantitative metabolite profiling in large-scale cardiovascular epidemiology at the European Atherosclerosis Society Congress in Glasgow, United Kingdom (22-25 March 2015). The conference will focus on the latest research in vascular disease research and lipid metabolism.

European Atherosclerosis Society Congress

9.2.2015
Dr Würtz on tour in Down Under (February 2015)


10 Feb 2015:
Dr Würtz is giving a talk entitled Quantitative metabolite profiling in large-scale cardiovascular epidemiology at the Menzies Institute for Medical Research, University of Tasmania.
Menzies Institute for Medical Research

20 Feb 2015:
Dr Würtz is giving a talk entitled High-throughput Metabolite Profiling of Cardiovascular Event Risk and Underlying Risk Factors at the South Australian Health and Medical Research Institute, Adelaide.
South Australian Health and Medical Research Institute

26 Feb 2015:
Dr Würtz is giving a talk entitled High-throughput Metabolite Profiling of Cardiovascular Event Risk and Underlying Risk Factors at the Department of Pathology, University of Melbourne.
Inouye Research Lab

27 Feb 2015:
Dr Würtz is giving a talk entitled Quantitative metabolite profiling in large-scale cardiovascular epidemiology at the Baker IDI Heart and Diabetes Institute, Melbourne.
Baker IDI Heart and Diabetes Institute

26.1.2015
Talk by Dr Kettunen (8 June 2015)

Dr. Kettunen has been invited to give a talk at the Royal Statistical Society, in London June 8th at "Hidden complexities in complex traits and genome wide association" workshop.

The website of the Royal Statistical Society

23.1.2015
Talk by Dr Würtz (22 June 2015 - 13.45-14.15)

Dr Würtz is giving an invited plenary lecture entitled Mendelian randomisation and metabolomics for risk factor profiling and drug development at the Mendelian Randomization Conference: From Population Health to Pharmaceutical Developments in Bristol, United Kingdom (21-24 June 2015). The conference will focus on the development, application and translation of Mendelian randomization methods to a diversity of fields, and with particular emphasis on discoveries in the pharmaceutical pipeline. Over the 3 days of this meeting, a programme of plenary, parallel and poster sessions will showcase the most recent research in the field.

The website of the Mendelian Randomization Conference

Conference flyer (PDF, 0.3 MB)

8.1.2015
An extensive work on metabolic profiling of cardiovascular risk published in Circulation

This is the largest metabolite profiling study in prospective cohorts (13,500 individuals with 1,740 incident events) and it identified 4 new biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.

P Würtz, AS Havulinna, P Soininen, T Tynkkynen, D Prieto-Merino, T Tillin, A Ghorbani, A Artati, Q Wang, M Tiainen, AJ Kangas, J Kettunen, J Kaikkonen, V Mikkilä, A Jula, M Kähönen, T Lehtimäki, DA Lawlor, TR Gaunt, AD Hughes, N Sattar, T Illig, J Adamski, TJ Wang, M Perola, S Ripatti, RS Vasan, OT Raitakari RE Gerszten, JP Casas, N Chaturvedi, M Ala-Korpela, V Salomaa Metabolite profiling and cardiovascular event risk: a prospective study of three population-based cohorts Circulation 131, 774-785, 2015

Press release:

New blood biomarkers predict future cardiovascular disease

A Finnish blood screening technology has uncovered four new biomarkers that improve the prediction of the risk for heart attack or stroke within the next 15 years. The blood profiling technique may eventually help doctors to identify those people who would benefit the most from early treatment.

An international research team led from Finland has discovered new blood biomarkers that improve prediction of the risk of cardiovascular disease. Blood samples of 13 441 apparently healthy people from Finland and the UK were screened for 68 biological markers. The health status of these volunteers were followed for over a decade. The researchers looked for measures in the blood that could reflect who had suffered a heart attack or a stroke within the following years. Four biomarkers were indicative of future cardiovascular disease risk independently of known risk factors. The study was published today in Circulation, the American Heart Association’s flagship journal.

The biomarkers for future cardiovascular disease were phenylalanine, a common amino acid, and the amount of monounsaturated fat in the blood; higher concentrations were linked with higher disease risk. These two biomarkers were as strong predictors of future heart disease as the measures of bad cholesterol or blood pressure. In addition, higher blood levels of both omega 3 and omega-6 fatty acids were linked with lower risk for cardiovascular disease. All these molecules are normally present in everyone’s blood, but it is the amount of these molecules that was shown to be reflecting the cardiovascular health.

- These new biomarkers can help to better assess the complex molecular processes behind the development of cardiovascular disease. The improved prediction of cardiovascular risk also suggests cost savings in healthcare by advanced biomarker profiling, says Dr. Peter Würtz, from the University of Oulu, Finland.

It is still unclear how the new molecular markers mediate the increased risk for cardio-vascular disease. The researchers are now working to uncover this aspect.
- The low-cost blood screening technology opens a treasure trove to understand the molecular mechanisms of heart disease and other metabolic diseases, says Dr. Würtz.

The scientific breakthrough was made possible thanks to the new blood screening technology, developed by the Computational Medicine Research Team in Finland. The method is based on Nuclear Magnetic Resonance (NMR) spectroscopy and enables determination of over 200 biomarkers for body metabolism from a single blood sample. The technique is now being used for metabolic screening in large population studies and biobanks across Europe.

The research was conducted in international collaboration, including researchers from the University of Oulu, the Finnish National Institute for Health and Welfare, the University of Eastern Finland, the University of Turku, the Framingham Heart Study in Boston, US, as well as the University College London, the London School of Hygiene and Tropical Medicine, and the University of Bristol, UK.



1.1.2015
Talk by Dr Soininen

Dr Soininen is giving an invited lecture entitled Six years of high-throughput serum NMR metabolomics ­towards large-scale epidemiology and genetics at the 36th Danish NMR meeting, Lund, Sweden, on 19th-21st January 2015.

Danish NMR meeting 2015

2014

18.12.2014
How media saw our work on the metabolic signatures of adiposity

Recently published study entitled Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change, PLOS medicine, resounded on the international media. Below a few selected links to the news items.

The New York Times, Daily Mail and Endocrine today, among others, wrote articles about the study:
The New York Times: Weight gain carriers risks, no matter your weight
Daily Mail: Why putting on just 1lb could be bad for your health - blood chemicals linked to heart disease, diabetes and liver problems increase with weight gain
Endocrine today: BMI increase adversely affects metabolic markers in lean young adults

In addition, Science Media Center collected a few expert comments about the publication in their website: Expert reaction to increased BMI and cardiometabolic risk markers , and Medical Research.com interviewed Dr Würtz about the background of the paper and future plans: MedicalRearch.com: Fat affects multiple metabolic pathways .

Myös suomalaisissa tiedotusvälineissä julkaisu huomioitiin. Mm. sanomalehti Kalevassa kerrottiin tutkimuksesta otsikolla Läski on vaaraksi myös terveelle nuorelle ja Iltasanomat julkaisi uutisen Tuore tutkimus selvitti: Jo pari liikakiloa on pahasta.

28-29.10.2014
Participation and talk by Dr Würtz

The Computational Medicine Team has been invited to attend the Think Tank on Metabolomics and Prospective Cohorts: How to Leverage Resources to be held in Rockville, Maryland, USA. The meeting is organised by the Division of Cancer Control and Population Sciences and the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. One of the aims of the meeting is to establish a collaborative consortium for those performing metabolomics analyses in prospective studies. The goal of this collaborative group is to tackle important scientific questions that cannot be addressed by one research group working independently. Dr Würtz is attending the meeting to represent the Computational Medicine Research Team and is giving a talk entitled Quantitative serum NMR metabolomics platform in epidemiology and genetics.

26.10.2014
Lipoprotein Subclass Metabolism in NASH; application of the Platform and a new NMR-method to quantify lipids in liver extracts – article in press in JLR

The serum NMR metabolomics platform was used to quantify 14 lipoprotein subclasses in serum samples at baseline and after obesity surgery. Additionally, a new NMR-method was set up to quantify several lipid molecules, e.g., free cholesterol and triglycerides, from extracted liver samples. Total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with non-alcoholic steatohepatitis (NASH). More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis and cell injury, independent of steatosis. Cholesterol concentration of all VLDL subclasses also associated with total and free cholesterol content in the liver. All NASH related changes in lipoprotein subclasses were reversed by obesity surgery.

VT Männistö, M Simonen, P Soininen, M Tiainen, AJ Kangas, D Kaminska, S Venesmaa, P Käkelä, V Kärjä, H Gylling, M Ala-Korpela, J Pihlajamäki Lipoprotein subclass metabolism in nonalcoholic steatohepatitis Journal of Lipid Research 55, 2676-84, 2014

23.10.2014
An extensive work on metabolic signatures of adiposity accepted for publication in PLOS Medicine

An extensive study with Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures across multiple metabolic pathways in 12,664 adolescents and young adults. Assesses also the effects of weight change beyond established risk factors. More information will be available at this site and from Dr Würtz and Prof Ala-Korpela when the actual publication time of the article is known and the embargo time has been released by PLOS Medicine. A news release will also be made.

P Würtz, Q Wang, AJ Kangas, RC Richmond, J. Skarp, M Tiainen, T Tynkkynen, P Soininen, AS Havulinna, M Kaakinen, JS Viikari, MJ Savolainen, M Kähönen, T Lehtimäki, S Männistö, S Blankenberg, T Zeller, J Laitinen, A Pouta, P Mäntyselkä, M Vanhala, P Elliott, KH Pietiläinen, S Ripatti, V Salomaa, OT Raitakari, MR Järvelin, G Davey Smith, M Ala-Korpela Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change PLoS Medicine 11, e1001765, 2014

Press release:

Excess body weight has negative metabolic effects in healthy young people with normal weight

A new Finnish blood screening technology reveals that increased body weight in the normal weight range causes negative metabolic effects in young adults. The adverse metabolic influences of excess body fat diminished by even a modest weight loss.

A large population study led by researchers at the Computational Medicine Research Team at the University of Oulu, Finland, has uncovered that the effects of having elevated BMI (body mass index) extends vastly beyond the impact on blood sugar and cholesterol levels, even in healthy adolescents and young adults in the normal BMI-range. By using a new molecular analysis technology and genetic information for 12,664 healthy volunteers, the researchers demonstrated that having higher BMI affects numerous metabolic markers reflecting the health state and risk for cardiometabolic diseases.

The results suggest that there is no threshold below which a BMI increase does not adversely affect the metabolic profile of an individual. Even for the people in the normal weight range, increased body weight will have adverse metabolic effects and increase the risk for cardiometabolic diseases. The study was published this week in the prestigious PLOS Medicine journal.

Despite the ongoing obesity epidemic, the fine-grained metabolic consequences of excess body weight remain unclear. Adverse effects of overt obesity are well known, but it is unclear if adiposity within the normal weight range affects the metabolic profile. The new study demonstrates that excess body weight causes chronic inflammation, adverse blood levels of branched-chain amino acids, and an altered balance of omega-fatty acids and sex hormones, in addition to the well-known effects on blood pressure and cholesterol.

- We have uncovered metabolic signatures of adiposity to an unprecedented molecular detail. The results help to clarify how increased BMI affects the risk for heart disease and diabetes. Not only for obese people, but rather in a continuous manner for the whole population, including those who are lean or overweight, says Dr. Würtz, Head of Molecular Epidemiology at the Computational Medicine Research Team.

In a further analysis Dr. Würtz and colleagues studied the change in BMI and cardiometabolic risk markers in 1,488 young adults over a 6 year period. The authors found that the metabolic risk profile of an individual was highly responsive to weight change over time.

- Even a modest weight loss was paralleled by favorable metabolic changes. This means that the high-risk cardiometabolic profile is not fixed once established, but can be reversed in early adulthood with the help of weight loss, Prof. Ala-Korpela continues.

The discoveries were made possible thanks to a new high-throughput blood screening methodology developed by the Computational Medicine Research Team. The method is based on Nuclear Magnetic Resonance (NMR) spectroscopy and enables determination of over 200 biomarkers for body metabolism from a single blood sample. It allows metabolic profiling in a very affordable manner and is therefore increasingly used for detailed metabolic screening in large population studies and biobanks across Europe.

The work was conducted in extensive international collaboration including researchers from, for example, University of Oulu, University of Eastern Finland, University of Turku, University of Tampere, Finnish Institute for Health and Welfare, and University of Bristol, UK.

16-17.10.2014
Talk by Dr Würtz (16 Oct 2014 - 13.00-14.00)

Dr Würtz is giving an invited lecture entitled Quantitative metabolic profiling in cardiovascular epidemiology and genetics at the Swedish Metabolomics Meeting, Malmö, Sweden.

Swedish Metabolomics Meeting 2014

15.10.2014
Dr Ville-Petteri Mäkinen appointed as an Associate Professor in the School of Molecular and Biomedical Science at University of Adelaide, Australia

Dr Ville-Petteri Mäkinen, a former member of the Computational Medicine Research Team, has been appointed as an Associate Professor in the School of Molecular and Biomedical Science at the University of Adelaide, Australia. Dr Mäkinen received his Doctor of Science degree in 2010 when working with us. Since then he has been working in the University of California, Los Angeles as well as at the Imperial College London and received a Postdoc Fellow from the American Heart Association. In 2014, he joined the South Australian Health & Medical Research Institute (SAHMRI) after receiving the prestigious position and funding to become an EMBL Australia Group Leader of Biomedical Informatics.

We would like to warmly congratulate Dr Mäkinen for his new appointment! We wish all the best for his new Molar (Molecular Life Course Research Group).

Prof Mäkinen is interested in developing statistical approaches to understand complex human phenotypes and diseases. He has published several key findings in the field, particularly related to type 1 diabetes and metabolic phenotyping of diabetic nephropathy. He is determined to pursue studies on molecular patterns that are indicative, predictive or causative for chronic age-related conditions such as obesity, diabetes and cardiovascular disease. This will also be the area of our future collaboration and we are most excited to have Prof Mäkinen and his team as one of our key collaborators in the future.

9-10.10.2014
Dos. Kettusen puheenvuoro

Dosentti Kettunen pitää esityksen aiheesta Vieläkö elät 5 vuoden kuluttua – testi tarjolla? Suomen Bioanalyytikkoliitto ry:n järjestämässä "Laboratoriolääketiede ja näyttely 2014" -tapahtumassa Helsingissä.

Laboratoriolääketiede ja näyttely 2014 -tapahtuman kotisivu

19.9.2014
Dr. Würtz featured in Science Magazine "What's Next In 'Omics: The Metabolome"

An article entitled What's Next In 'Omics: The Metabolome in Life Science Technologies (produced by the Science/AAAS, written by Chris Tachibana) underlines the significance of metabolomics as an immediate measure of physiology. The article describes research, instruments, and the challenges of the metabolomics. "Metabolomics is becoming part of every researcher's toolkit", says associate professor Ute Roessner, from University of Melbourn in the article.

The article also refers to the Computational Medicine Research Team: "Peter Würtz, head of molecular epidemiology, University of Oulu, Finland, recently coauthored a paper that applied NMR metabolomics using Bruker instruments to thousands of Estonian and Finnish biobank samples. The research team discovered that four biomarkers, when combined, are significantly associated with increased risk of short-term death from all causes. The study was observational, with no exploration of mechanisms, notes Würtz, but shows the power of NMR for biomarker analysis."

The article is available here.

15-19.9.2014
Talk by Dr Würtz

Dr Würtz is giving an invited lecture entitled Risk factor profiling by quantitative NMR metabolomics: applications to insulin resistance and obesity at the European Association for the Study of Diabetes Meeting, Vienna, Austria.

8.-9.9.2014
Talk by Dr Kettunen

Dr Kettunen is giving a talk at the MRC Integrative Epidemiology Unit in Bristol at the Workshop on Instrumental Variables and Related Methods Sep 8-9 2014. The title of Dr Kettunen’s talk is Mendelian randomisation in molecular systems: assessing causality between gene expression and metabolites.

30.8.-3.9.2014
Talk by Prof Ala-Korpela (2 Sep 2014 - 11:22)

Prof Ala-Korpela is giving an invited talk entitled Metabolomic approach for biomarker screening in the European Society of Cardiology (ESC) Congress 2014, in the session focusing on Novel circulating biomarkers predicting atherosclerosis, in Barcelona, Spain. The Congress is expected to be a true representation of scientific developments in the field; a record number of 11,444 abstracts from 100 countries have been submitted.

The website of ESC Congress 2014.

21.8.2014 Article published in Nature Communications
A metabolic view on menopause and ageing

The Computational Medicine Research Team has co-authored a research entitled A metabolic view on menopause and ageing, published in Nature Communications on 21 Aug 2014.

We are facing substantial social, economic and health-care issues globally with aging populations. Aging relates to a wide spectrum of metabolic and other chronic diseases. The disease burden significantly differs by age and sex. Menopause is an endocrinological transition strongly influencing health and disease susceptibility of all middle-aged and elderly women. Menopause has substantial health consequences ranging from disturbances in lipid and glucose metabolism to psychological stress and sleep alterations. Importantly, menopause is also closely linked with cardiovascular diseases, the leading cause of death worldwide. Detailed molecular understanding of the effects of aging and menopause is therefore of utmost importance.

Utilising the serum NMR metabolomics platform, developed by the Computational Medicine Research Team, we now shed new light on age-related metabolic consequences in 26,065 individuals of Northern European ancestry. Age-specific metabolic fingerprints differ significantly by gender and, in females, a substantial atherogenic shift overlapping the time of menopausal transition is observed. In meta-analysis of 10,083 women, menopause status associates with amino acids glutamine, tyrosine and isoleucine, along with serum cholesterol measures and atherogenic lipoproteins. Among 3,204 women aged 40­-55 years, menopause status associates additionally with glycine and total, monounsaturated, and omega-7 and -9 fatty acids. In addition to lipid alterations, menopause may contribute to future metabolic and cardiovascular risk via influencing amino acid concentrations, adding to the growing evidence of the importance of amino acids in metabolic disease progression.

These new findings demonstrate that metabolic fingerprints are strongly age- and sex-dependent. Men enter the pro-atherogenic phase already in the early middle age. In women, a clear atherogenic shift overlapping the menopausal transition is observed. Our findings of a menopause-specific increase regarding several amino acids and fatty acids suggest a menopausal influence on numerous pathways contributing to the pathogenesis of diabetes and cardiovascular diseases.

The detailed new molecular findings illustrate the power and potential of the serum NMR metabolomics platform in population epidemiology and suggest an influential role for this cost-effective technology in biobanking and clinical biomarker arena. This automated platform provides quantitative molecular information for over 200 metabolic measures , including the lipid concentrations and composition of 14 lipoprotein subclasses, various fatty acids, amino acids, glycolysis related measures and ketone bodies. The molar concentrations of these measures are obtained from a single serum sample with costs comparable to standard lipid measurements.

K Auro, A Joensuu, K Fischer, J Kettunen, P Salo, H Mattsson, M Niironen, J Kaprio, JG Eriksson, T Lehtimäki, O Raitakari, A Jula, A Tiitinen, M Jauhiainen, P Soininen, AJ Kangas, M Kähönen, AS Havulinna, M Ala-Korpela, V Salomaa, A Metspalu, M Perola A metabolic view on menopause and ageing Nature Communications 5, 4708, 2014

3.7.2014
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk entitled Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics in the European Society of Cardiology Working Group, Atherosclerosis and Vascular Biology, Satellite Symposium on Circulating Biomarkers for Cardiovascular Disease for the Frontiers in CardioVascular Biology 2014 Meeting in Barcelona, Spain.

Symposium on Circulating Biomarkers in Atherosclerosis

12-13.6.2014
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk entitled Computational medicine: a multidisciplinary and global endeavour to understand health and disease aetiology in the Conference on Epidemiological Birth Cohort Studies, dedicated to the memory of Professor Paula Rantakallio, University of Oulu, Oulu, Finland.

5.6.2014
Talk by Dr Kettunen

Dr Kettunen is giving an invited talk entitled The role and importance of quantitative serum NMR metabolomics in genetics and systems biology in the XXXVI Finnish NMR symposium, organised by the Finnish NMR Society and the University of Oulu, in Syöte, Finland.

5.6.2014
Talk by Dr Würtz

Dr Würtz is giving an invited talk entitled Quantitative serum NMR metabolomics in large population studies: Improved understanding of heart disease and diabetes in the XXXVI Finnish NMR symposium, organised by the Finnish NMR Society and the University of Oulu, in Syöte, Finland.

11.5.2014
The Finnish Diabetes Research Foundation Grant for Computational Medicine

Dr Peter Würtz, Head of Molecular Epidemiology at Computational Medicine, has been awarded a research grant of 25,000€ from The Finnish Diabetes Research Foundation for investigations of metabolic reflections of the risk for type 2 diabetes in young adults.

3.5.2014
Emil Aaltonen Grant for Computational Medicine

Dr Tuulia Tynkkynen, Postdoctoral Fellow in Metabolomics in the Kuopio Campus at UEF, has been awarded a research grant of 24,950 € from the Emil Aaltonen Foundation to support the development of quantitative and high-throughput NMR metabolomics towards epidemiological applications.

6.4.2014
Professori Ala-Korpelan haastattelu sanomalehti Kalevassa: "Hypoteesiton tutkimus uutta"

4.4.2014
Talk by Dr Kettunen

Dr Kettunen is giving a talk entitled Omics in YFS - mechanisms underlying biomarkers of death in the LASERI Symposium in Turku University Hospital, Turku, Finland.

4.4.2014
Talk by Dr Würtz

Dr Würtz is giving a talk entitled NMR metabolomics in YFS: what's going on in the LASERI Symposium in Turku University Hospital, Turku, Finland.

26.3.2014
Computational Medicine article in PLOS Medicine selected for F1000Prime

The article co-led by the Computational Medicine Research Team entitled "Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons” published in PLOS Medicine Feb 25 2014 has been selected for F1000Prime.

The article was recommended as being of special significance in its field by F1000Prime Members Dr Panayiotis Benos from University of Pittsburgh and Dr Michael Kurilla from National Institutes of Health, USA.

"This is the first application of high-throughput technology to identify biomarkers predictive of all-cause mortality and the results are very encouraging and consistent between the two cohorts”, Dr Benos reviewed. Dr Kurilla further described the utility of the high-throughput profiling technology: "While the potential for a composite assessment of frailty cannot be understated, of more general applicability is their methodology for rapidly identifying biomarkers in large samples. This approach could lead to utlilization during natural history studies to identify and validate candidate biomarkers for objective endpoint of future drug and vaccine trials. Another application would be the ability to quickly identify biomarkers related to adverse events with the potential to better understand mechanisms of toxicity."

19.3.2014
Sigrid Jusélius Foundation funds Computational Medicine

Prof Ala-Korpela, as the Head of the Computational Medicine Research Team, was awarded a 3-year research grant from the Sigrid Jusélius Foundation in 2013 for the research entitled "Life-course metabolic health – population-wide metabolite profiling of cardiometabolic diseases"; the 2014 part of the grant will be 55,800 € for the period of 1.5.2014-30.4.2015.

1.3.2014

Kuolinriskin ennustaminen on kansainvälistä kärkitiedettä

Professori Mika Ala-Korpelan ja tutkimusprofessori Markus Perolan mielipidekirjoitus Helsingin Sanomissa 1.3.2014.

Lue juttu tästä (aukeaa uuteen ikkunaan)

27.2.2014
Dr Kettunen was just interviewed by Voice of America

"VOA provides a wide range of programming for broadcast on radio, TV and the internet outside of the U.S., in 43 languages. VOA produces about 1,500 hours of news and feature programming each week for an estimated global audience of 123 million people."

VOA: New Blood Test Predicts Five-Year Mortality

27.2.2014
Professori Ala-Korpelan haastattelu Iltalehdessä

Klikkaa kuvaa suurentaaksesi (aukeaa uuteen ikkunaan).

27.2.2014
Professori Ala-Korpelan haastattelu sanomalehti Kalevassa

Klikkaa kuvaa suurentaaksesi (aukeaa uuteen ikkunaan).

26.2.2014
Dr Johannes Kettunen interviewed on BBC Radio Scotland on 26.2.2014 at 17:00
26.2.2014
Dr Johannes Kettunen interviewed live on BBC London on 26.2.2014 at 09:00
26.2.2014
Professori Ala-Korpelan haastattelu Yle Radio Suomen Ajantasa-ohjelmassa 26.2.2014 klo 10.03
25.2.2014 Article published in PLOS Medicine
NMR-metabolomics revealed new blood biomarkers to predict death

The Computational Medicine Research Team has co-authored, Prof Ala-Korpela being one of the leaders, a research entitled Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons, published in PLOS Medicine on 25 Feb 2014.

In hypothesis-free analyses we recently encountered an intriguing finding: among the metabolic measures quantified by the serum NMR metabolomics platform, we found four biomarkers that are predictive for all-cause mortality. Early and accurate identification of high-risk individuals, who appear healthy, but in fact have an underlying serious illness, would provide a rationale for further medical assessments and valuable opportunities for preventive treatments. Currently there is no such test that could accurately assess whether a person is at risk of ill health generally, or likely to die soon from a disease. Thereby our unforeseen finding of four biomarkers that predict the risk of short-term death (within 5 years) among a general population, rather than within people already known to be ill, is of high clinical importance. The finding was based on two large population based cohorts, a discovery cohort of almost 10,000 Estonian individuals and a replication cohort of around 7,500 Finnish people. The four biomarkers – glycoprotein, albumin, VLDL particle size, and citrate – are implicated in various pathophysiological mechanisms including inflammation, fluid imbalance, lipoprotein metabolism, and metabolic homeostasis. While these findings raise more questions than they provide answers, they are likely to open a new path to unravel novel relationships between systemic biomarkers and diverse morbidities.

K Fischer, J Kettunen, P Würtz, T Haller, AS Havulinna, AJ Kangas, P Soininen, T Esko, ML Tammesoo, R Mägi, S Smit, A Palotie, S Ripatti, V Salomaa, M Ala-Korpela, M Perola, A Metspalu Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons PLoS Medicine 11, e1001606, 2014

18.2.2014
Plenary talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited plenary talk entitled Computational medicine: a multidisciplinary and global endeavour to understand health and disease aetiology in the 11th Science Day of the Faculty of Medicine, University of Oulu, Oulu, Finland.

1.2.2014
MScEng Teemu Suna joins the Computational Medicine Team in Oulu

MScEng Teemu Suna joins the Computational Medicine Research Group as the Head of Health Technology. Recent scientific findings and publications by the Team suggest that computational medicine is likely to have a key role in helping to solve population scale health challenges. This trend calls for an even more multidisciplinary approach to computational medicine.

Teemu has 15 years of experience in various engineering and business positions in the area of information technology. He has pioneered in several areas of healthcare IT and is an expert in healthcare applications, technology ventures and innovation management. The last three years he worked as a Chief Technology Officer at Fujitsu Finland Oy in Helsinki focusing on the IT challenges of national healthcare.

"I see this as a great opportunity to create applications arising from world-class science. I am excited to join the Computational Medicine Team and the endeavours to do great science aiming to enable the new era of health care solutions. I see this as an exceptional undertaking to combine scientific research and public health perspectives into something concrete. I’m very excited to be a part of the Team", Teemu Suna says.

The Computational Medicine Research Team warmly welcomes Teemu!

10.1.2014
ALSPAC awarded £7.9 million funding from Medical Research Council and Wellcome Trust

The Avon Longitudinal Study of Parents and Children (ALSPAC) has been awarded £7,9 million core funding from MRC and Wellcome Trust. The funding is for the period April 2014 to March 2019. ALSPAC also receives financial support from the University of Bristol.

From April, ALSPAC's scientific director, Professor George Davey Smith, who leads on scientific innovation, will be joined by a co-PI, Professor Paul Burton, who will be responsible for the cohort infrastructure.

This five-year funding stream will:

  • support research and lab infrastructure, ensuring researchers have access to data and samples for their own research
  • sustain cohort maintenance, ensuring as many participants as possible continue to take part in the study
  • enable new data collection on the original study children (and their children) via clinical assessment at age 24/5 and two questionnaires
  • allow for the consolidation of genetic data by genotyping all study participants
  • support the data linkage programme

Prof Mika Ala-Korpela, Head of the Computational Medicine Research Team and also Prof of Computational Medicine in the University of Bristol, was a co-applicant in the funding applications and is a co-investigator in ALSPAC leading the related metabolomics and computational medicine.

More information at http://www.bristol.ac.uk/alspac/

2013

20.12.2013
Dr Soininen appointed in the University of Eastern Finland

Dr Pasi Soininen has been appointed as an Assistant Professor of Pharmaceutical Chemistry at the University of Eastern Finland, School of Pharmacy starting on January 1st 2014.

16.-17.12.2013
A keynote lecture on scientific methodology by Dr Würtz

Dr Würtz is giving a keynote lecture on scientific methodology, entitled High-throughput serum NMR metabolomics – towards multi-species systems epidemiology to understand common metabolic disorders, in the Annual Academic Meeting of the Royal College of Obstetricians and Gynecologists in London, UK.

15.12.2013
Dr Johannes Kettunen joins the Computational Medicine Team in Oulu

Dr Johannes Kettunen is recruited to the University of Oulu, Institute of Health Sciences to join the Computational Medicine Research Group as the Head of Genetics. Dr Kettunen holds an Academy of Finland Postdoctoral Researcher position and is a renowned scientist in the area of metabolic genetics. He has led various studies that link metabolic and genetic aspects for cardiometabolic diseases and published almost 40 articles in international peer-reviewed journals; several recent articles have appeared in Nature Genetics, PLOS Genetics and PLOS Medicine. We are proud to welcome Johannes to the Team!

26.11.2013
Talk by Dr Würtz

Dr Würtz is giving an invited talk entitled High-throughput Metabolite Profiling of Serum – Towards Systems Epidemiology of Cardiometabolic Diseases at Leiden University Medical Center, Leiden, The Netherlands.

19.11.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled Metabolite Profiling Identifies Novel Biomarkers for Cardiovascular Disease Risk Across Multiple Population-Studies and Profiling at the American Heart Association Sessions, Dallas, Texas.

15.11.2013
British Heart Foundation Special Project Grant for Serum NMR Metabolomics

The University College-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium of prospective population studies is a well-known collection of epidemiological cohorts that provides a powerful resource for integrated genomic and biomarker research. The British Heart Foundation now funds, via a Special Project Grant, extensive work that aims for cardiometabolic disease prediction, causal analysis and drug development using serum NMR metabolomics data via the special platform developed by the Computational Medicine Research Team. The BHF funding for this 3-y project, led by Prof Aroon Hingorani at UCL, is around £800,000. Prof Ala-Korpela, Head of the Computational Medicine Research Team, was a co-applicant in the application. Prof Hingorani and the UCLEB Consortium are long-term key collaborators of the Computational Medicine Research Team.

15.11.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk entitled High-throughput serum NMR metabolomics – systems epidemiology with clinical potential in the Meeting of the Finnish Pharmacological Society, University of Oulu, Finland.

10.10.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a lecture on Computational medicine: a multidisciplinary and global endeavour to understand health and disease aetiology in the Netherlands Metabolomics Centre workshop Towards European Metabolomics Initiatives in Noordwijk aan Zee, The Netherlands.

18.9.2013 Article published in Journal of the American College of Cardiology
Metabolomics to aid Mendelian randomization studies

Mendelian randomization is increasingly used to infer causality in observational epidemiology. Confounding factors are then minimized through the random assignment of genetic predisposition. In this work we illustrated that lipoprotein subclass profiling reveals vast pleiotropy in the genetic variants of lipid risk factors for coronary heart disease. Caution must therefore be exercised when addressing causality of lipid fractions when using these genotypes in instrumental analyses. More detailed phenotyping, such as lipoprotein subclass profiling, would therefore be advised in addressing the validity of the genetic instruments used in Mendelian randomization. This is increasingly important because Mendelian randomization is becoming a widespread tool for causal inference, and guidelines are placing evidence from such studies between observational data and randomized trials.

P Würtz, AJ Kangas, P Soininen, T Lehtimäki, M Kähönen, JS Viikari, OT Raitakari, MR Järvelin, G Davey Smith, M Ala-Korpela Lipoprotein subclass profiling reveals pleiotropy in the genetic variants of lipid risk factors for coronary heart disease: a note on Mendelian randomization studies JACC – Journal of the American College of Cardiology 62, 1906-8, 2013

31.8.- 4.9.2013
A presentation by Dr Würtz

Dr Würtz is giving a talk entitled Role of metabolomics and genomics in delivering early interventions in the European Society of Cardiology (ESC) Congress 2013 in Amsterdam, The Netherlands.

29.8.2013
Novo Nordisk Foundation funds Computational Medicine

Prof Ala-Korpela, as the Head of the Computational Medicine Research Team, has been awarded a 1-year research grant of DKK 450.000 (~60.000 euros) from the Nordic Research Committee of the Novo Nordisk Foundation to support the project entitled "Comprehensive metabolic profiling of glucose tolerance – Molecular characterization of the response to a glucose challenge in the Northern Finland Birth Cohort".

8.7.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a lecture on High-throughput metabolic phenotyping of serum – towards systems epidemiology of common metabolic disorders in the Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK.

28.-29.6.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a lecture on High-throughput metabolic phenotyping of serum – new insights into epidemiology and genetics in the 1st Meeting of the International Spine and Pain Consortium (ISPC) – "Phenotypes Revisited" in Hong Kong.

28.6.2013
A presentation by Dr Würtz

Dr Würtz is giving a talk entitled Computational medicine and the global health care challenge in the 8th World Conference of Science Journalists – Post Congress Excursion Tour to the University of Oulu, Finland.

21.5.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a lecture on High-throughput serum NMR metabolomics – systems epidemiology with clinical potential in King's College & St.Thomas' Hospital in London, UK.

18.5.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled Metabolite signatures of insulin resistance in young adults – metabolite profiling in population-based cohorts at the Scandinavian Society for the Study of Diabetes Meeting, Espoo, Finland.

13.-14.5.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk on High-throughput metabolic phenotyping of serum – towards systems epidemiology of common metabolic disorders in the Belgian Metabolomics Society and the Netherlands Metabolomics Centre Joint Scientific Meeting in Spa, Belgium.

26.-28.4.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on Metabolomics, new insights for genetics and epidemiology in the Scientific collaboration meeting between University College London & Karolinska Institutet, Cumberland Lodge in Windsor, West Berkshire, UK.

25.4.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled Metabolite profiling by high-throughput serum NMR mebolomics – applications to Mendelian Randomisation at University of Bristol, Bristol, UK.

17.4.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled A high-throughout platform for metabolomics in large-scale population studies - etiological insights and prediction of metabolic diseases at the Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.

16.4.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled Metabolite profiles characterising obesity: observational and genetic evidence in 15,000 young adults at the Scandinavian Society for Atherosclerosis Research, Copenhagen, Denmark.

27.3.2013
Sigrid Jusélius Foundation funds Computational Medicine

Prof Ala-Korpela, as the Head of the Computational Medicine Research Team, has been awarded a 3-year research grant from the Sigrid Jusélius Foundation for the research entitled "Life-course metabolic health – population-wide metabolite profiling of cardiometabolic diseases"; the 2013 part of the grant is 56,000 € for the period of 1.5.2013-30.4.2014.

21.3.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics - from systems epidemiology to the clinic? Biocenter Oulu Seminar Series, University of Oulu & Biocenter Oulu, Finland.

15.3.2013
Talk by Dr Würtz

Dr Würtz is giving a talk entitled High-Throughput Metabolite Profiling in Cardiovascular Epidemiology at the Finnish Society for Atherosclerosis Research, Turku, Finland.

14.3.2013
Integrative Epidemiology Unit at the University of Bristol

UK Medical Research Council has awarded £10.5M funding for the new MRC University of Bristol Integrative Epidemiology Unit (IEU). The MRC funding is supplemented by £12.5M from the University of Bristol. IEU is to be established 1 June 2013 onwards and the first funding period will be 5 years. UNITE will be led by Prof George Davey Smith and it includes six interrelated research programmes:

  • From Mendelian Randomization to Hypothesis-Free Causal Inference – led by Prof George Davey Smith
  • Epigenetic Epidemiology – led by Prof Caroline Relton
  • Causal Analyses, Statistical Efficiency and Phenotypic Precision Through Study Design: Recall by Genotype – led by Dr Nicholas Timpson
  • Using Genetics to Identify Causal Pathways that Influence Bone Related Phenotypes in Children and Young Adults – led by Dr David Evans
  • Integrative Epidemiology to Understand Causal Relationships between Women¹s Reproductive Health and Cardiometabolic Health – led by Prof Debbie A Lawlor
  • Determinants, Consequences and Modification of Health Behaviours – led by Prof Marcus Munafò

UNITE involves a set-up of a Metabolomics Core Facility at the University of Bristol including two high-throughput NMR spectrometers initially focused to apply the serum NMR metabolomics platform developed by the Computational Medicine Research Team in Finland. Prof Ala-Korpela was one of the applicants being named as a key IEU staff member and is leading the Metabolomics Core Facility at the University of Bristol.

7.3.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – systems epidemiology with clinical potential in the University of Tromsø, Department of Community Medicine in Tromsø, Norway.

19.2.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – systems epidemiology with clinical potential in the University of Umeå, Sweden.

7.2.2013
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on Lots of people & experiments – computational medicine in the XII Lääketieteellisen fysiikan ja tekniikan päivät, University of Oulu, Finland.

18.1.2013 Article published in Journal of Internal Medicine
Triglyceride-cholesterol imbalance predicts diabetic kidney disease and mortality in type 1 diabetes

Circulating cholesterol and triglyceride levels have been associated with vascular injury in type 1 diabetes. Lipoproteins are responsible for transporting lipids, and alterations in their subclass distributions may partly explain the increased mortality in individuals with type 1 diabetes. In this study 3,544 individuals with type 1 diabetes were recruited by the nationwide multicentre FinnDiane Study Group. Lipoprotein subclass concentrations were measured by proton NMR spectroscopy and multivariate phenotyping was utilised with self-organising maps.

The combination of low serum cholesterol and low triglycerides indicated the most favourable lipoprotein phenotype. If serum lipids were elevated, a high triglycerides/cholesterol ratio denoted the high-risk phenotype with poor glycaemic control, excess body weight and hypertension. Our detailed analyses revealed that the imbalance between cholesterol and triglycerides affects the whole of lipoprotein metabolism simultaneously. Therefore, it is not sufficient to focus on the established risk factors such as LDL cholesterol, but anti-atherogenic interventions in type 1 diabetes should target all the lipoprotein subclasses to negate the effects of any structural and compositional abnormalities due to the diabetic milieu. It is also noteworthy that a safe triglyceride concentration may be much lower in type 1 diabetes than in the general population.

VP Mäkinen, P Soininen, AJ Kangas, C Forsblom, N Tolonen, LM Thorn, J Viikari, OT Raitakari, M Savolainen, PH Groop, M Ala-Korpela Triglyceride-cholesterol imbalance across lipoprotein subclasses predicts diabetic kidney disease and mortality in type 1 diabetes: the FinnDiane Study Journal of Internal Medicine 273, 383-95, 2013

15.1.2013
New spectrometer operational

The installation of the new 600 MHz spectrometer at the University of Eastern Finland was finalised a few days ago and now the spectrometer is operational. It will double the throughput of the laboratory up to 80,000 serum samples in a year.

2012

20.12.2012 Article published in Circulation
Serum NMR-metabolomics brings metabolic effects of physical activity to light

In a recent paper published in Circulation we detail findings that numerous molecular differences in the circulating metabolome indicate better metabolic health in the physically active than in inactive individuals.

In relation to this paper, Circulation published an editorial by Susan Cheng entitled Interrogating the age-old wisdom of exercise; Circulation 127, 311-313, 2013.

Selected text from the editorial: “Kujala and colleagues report intriguing results from the first long-term study of metabolite profiles associated with persistent physical activity. The authors used NMR spectroscopy to perform a targeted assay of metabolites that included amino acids, ketone bodies, glycolytic precursors, and lipid particles. Sixteen adult twin pairs were identified for their marked intra-pair discordance in daily leisure-time physical activity of up to 12 METS per day, over up to three decades of follow up, and then had metabolite profiling performed. In addition, a total of 1037 age- and sex-matched pairs of unrelated adults from 3 community-based cohorts were identified as persistently active or persistently inactive; these individuals also underwent metabolite profiling. The main findings of the study were three-fold. First, the authors noted that active compared to inactive individuals had better lipoprotein cholesterol profiles and higher levels of polyunsaturated relative to saturated fatty acids. Second, they found that the branched chain amino acid (BCAA) isoleucine was lower in active than inactive individuals, with similar findings for valine as well as tyrosine and phenylalanine. Finally, they observed that alpha1-acid glycoprotein, an acute phase reactant, was lower in persistently active than in persistently inactive individuals. The findings overall are noteworthy for several reasons. Importantly, the main results were remarkably consistent and in the expected direction across all 4 study cohorts despite differences between the cohorts in mean age, the instruments used to assess physical activity, and the durations of follow up. The results are also informative. Compared to mass spectrometry, NMR spectroscopy has a lower sensitivity for detecting less abundant metabolites. Nonetheless, NMR was used to effectively identify metabolites associated with exercise from across multiple functional domains, including lipid metabolism, amino acid metabolism, and inflammation. The relation of more optimal lipid profiles with long-term physical activity is not surprising and could be considered an experimental control. On the other hand, the observed relation of lower isoleucine with physical fitness is novel. // By integrating the influences of active endogenous and exogenous factors at a given point in time, a whole body metabolite profile could eventually offer up-to-date, individual-specific data that are useful not only for characterizing risk for disease and determining potential for risk reduction – but also for tailoring a prescription for intervention.”

UM Kujala, VP Mäkinen, I Heinonen, P Soininen, AJ Kangas, TH Leskinen, P Rahkila, P Würtz, V Kovanen, S Cheng, S Sipilä, M Hirvensalo, R Telama, T Tammelin, MJ Savolainen, A Pouta, PF O'Reilly, P Mäntyselkä, J Viikari, M Kähönen, T Lehtimäki, P Elliott, MJ Vanhala, OT Raitakari, MR Järvelin, J Kaprio, H Kainulainen, M Ala-Korpela Long-term leisure-time physical activity and serum metabolome Circulation 127, 340-8, 2013

17.12.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – from systems epidemiology to the clinic?
UCL Institute of Cardiovascular Science, University College London, UK.

26.11.2012
Infrastructural funding for Computational Medicine

In the latest infrastructure funding round for 2013 the Research Council of the University of Oulu, together with the Faculty of Medicine, has awarded Prof Ala-Korpela and the Computational Medicine Research Team 500,000 € to set up a new NMR metabolomics laboratory at the University of Oulu, Oulu, Finland.

20.11.2012
Prof Ala-Korpela appointed in the University of Bristol

Dr Mika Ala-Korpela has been appointed part-time as a Professor of Computational Medicine at the School of Social and Community Medicine, University of Bristol, Bristol, UK starting on 1 January 2013. Professor Ala-Korpela will be leading the forthcoming Metabolomics Core Facility at the University of Bristol. Incorporation of epidemiological metabolomics relates to the strategic scientific aims of research led by Professor George Davey Smith, including application and development of causal methodologies to answer key questions in the area of cardio-metabolic ill-health and translation of the findings and methodologies into clinical and public health practice.

29.-30.10.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk on High-throughput serum NMR metabolomics – the new era in epidemiology & genetics in the Metabolomics Workshop, Swedish NMR Centre, University of Gothenburg, Sweden.

22.10.2012
Prof Ala-Korpelan haastattelu Aktuumissa

"Uuden alan pioneeri"Prof Ala-Korpelan haastattelu Oulun Yliopiston Aktuumi-lehden numerossa 4/2102.

20.-21.9.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk on High-throughput serum NMR metabolomics – epidemiology in the biobanking era in the Biobanks and International Biobank Summit: Future Directions Conference, Uppsala University, Sweden.

11.9.2012
CONACYT funding for collaboration in México

The Mexican Council of Science and Technology (CONACYT) has funded a collaboration with Prof Carlos Alberto Aguilar Salinas (Instituto Nacional de Ciencias Médicas y Nutrición, México) and Prof Ala-Korpela in the project studying the incidence of the metabolic syndrome, type 2 diabetes and cardiovascular events in 12,000 adults living in central Mexico; around 130,000 € funding was obtained for serum NMR metabolomics.

16.8.2013 Article published in PLOS Genetics
Triglyceride-cholesterol imbalance predicts diabetic kidney disease and mortality in type 1 diabetes

The Computational Medicine Research Team has published with colleagues from, for instance, the Medical Systems Biology, Departments of Pathology and of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia & the Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA a research entitled “Novel loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis”, published in PLOS Genetics 8, e1002907, 2012.

In this study, we aimed to identify novel genetic variants for metabolism, characterize their effects on nearby genes, and show that the nearby genes are associated with metabolism and atherosclerosis. To discover new genetic variants, we used an alternative approach to traditional genome-wide association studies: we leverage the information in phenotype covariance to increase our statistical power. We analysed 6,600 individuals from two population-based cohorts with both genome-wide SNP data and serum NMR metabolomics profiles. From the observed correlation structure of 130 quantified metabolites, we identified 11 metabolic networks and performed a multivariate genome-wide association analysis.

We identified 34 genomic loci at genome-wide significance, of which 7 were novel. In comparison to univariate tests, multivariate association analysis identified nearly twice as many significant associations in total. Multi-tissue gene expression studies identified variants in our top loci, SERPINA1 and AQP9, as eQTLs and showed that SERPINA1 and AQP9 expression in human blood was associated with metabolites from their corresponding metabolic networks. The liver expression of AQP9 was associated with atherosclerotic lesion area in mice, and in human arterial tissue both SERPINA1 and AQP9 were shown to be upregulated in atherosclerotic plaques.

This study illustrates that multivariate analysis of correlated metabolites can boost power for gene discovery substantially. Further functional work will need to be performed to elucidate the biological role of SERPINA1 and AQP9 in atherosclerosis.

M Inouye, S Ripatti, J Kettunen, LP Lyytikäinen, N Oksala, PP Laurila, AJ Kangas, P Soininen, MJ Savolainen, J Viikari, M Kähönen, M Perola, V Salomaa, O Raitakari, T Lehtimäki, MR Taskinen, MR Järvelin, M Ala-Korpela, A Palotie, PI de Bakker Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis PLoS Genetics 8, e1002907, 2012

27.7.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR – the new era in epidemiology & genetics in the Institute of Cardiovascular & Medical Sciences BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK.

27.7.2012 Article published in Journal of Internal Medicine
Abnormal glucose tolerance affects lipoprotein subclass profiles and particles

The Computational Medicine Research Team has published a large population-based study on glucose tolerance and lipoprotein metabolism together with the Research Group led by Academy Professor Markku Laakso at the University of Eastern Finland and the Kuopio University Hospital. The research was entitled “Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: A population-based study of 9,399 Finnish men” and published in the Journal of Internal Medicine 272, 562-572, 2012.

We investigated serum concentrations of lipoprotein subclass particles and their lipid components determined by proton NMR spectroscopy. Abnormal glucose tolerance (especially isolated impaired fasting glucose and newly diagnosed type 2 diabetes) was significantly associated with increased concentrations of VLDL subclass particles and most of their lipid components. There was a consistent trend towards a decrease in large and an increase in small HDL particle concentrations in individuals with hyperglycaemia even after adjustment for serum total triglycerides and HDL cholesterol. Abnormal glucose tolerance modifies the concentrations of lipoprotein subclass particles and their lipid components in the circulation and is also related to compositional changes in these particles.

J Wang, A Stančáková, P Soininen, AJ Kangas, J Paananen, J Kuusisto, M Ala-Korpela, M Laakso Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population-based study of 9399 Finnish men Journal of Internal Medicine 272, 562-72, 2012

13.7.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR – the new era in epidemiology & genetics in the Institute Physico-Chemical Medicine in Moscow, Russia.

1.-5.7.2012
A talk by Dr Würtz

Dr Würtz is giving a talk entitled High-throughput serum NMR – the new era in epidemiology & genetics in the EUROMAR Conference, University College Dublin, Ireland.

18.-20.6.2012
A talk by Dr Würtz

Dr Würtz is giving a talk entitled High-throughput serum NMR metabolomics in cardiovascular epidemiology in the 15th Kuopio Bio-NMR Workshop: Cardiac magnetic resonance imaging and applications. A.I.Virtanen Institute, University of Eastern Finland, Kuopio, Finland.

25.5.2012
EFSD funding for collaboration with the Estonian Biobank

The European Foundation for the Study of Diabetes (EFSD) New Horizons Collaborative Research Initiative funding of 100,000 € for the project Genomic, metabolomic and demographic characteristics of type 2 diabetes in the Estonian population (5/2012–4/2013) has been obtained in collaboration with Prof Andres Metspalu (Director of the Estonian Genome Center, University of Tartu, Estonia) and Prof Ala-Korpela.

22.5.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – the new era in epidemiology & genetics in the Richard Doll Seminars in Public Health and Epidemiology, University of Oxford, UK.

3.5.2012
TEKES funding for Computational Medicine

The INDICO-project, Individualized Connected Health, has received a positive decision from TEKES, the Finnish Funding Agency for Technology and Innovation, for the funding of 350,000 € for 8/2012 – 12/2013; Prof Ala-Korpela is the leader of the subproject Metabolomics in Individual Healthcare. The project aims to evaluate new viewpoints on health care concepts and individualised health and wellbeing. The focus is set on assessment and prediction of health risks and improving our understanding on metabolic diseases and their aetiology (rather than on treatment or diagnostics of diseases). A multidisciplinary approach will be taken to widely appreciate the aspects how individuals could promote their health with the knowledge of their timely personal data. New means will be explored to collect, save and analyse metabolic and life style data in relation to preventive health care together with economic evaluations of setting up optimised societal as well as personal priority strategies.

2.5.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – towards epidemiological systems biology in Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School in Rotterdam, The Netherlands.

26.-29.4.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving an invited talk on Metabolic profiling and hypertension in the 22nd Scientific Meeting of the European Society of Hypertension (ESH), ExCeL in London, UK.

17.4.2012 Article published in Diabetes
Metabolic signatures may help to promote lifestyle habits for prevention of type 2 diabetes

The Computational Medicine Research Team has published a pioneering research entitled “Metabolic signatures of insulin resistance in 7,098 young adults” in Diabetes.

This is one of the first applications of comprehensive serum metabolomics in large population-based cohorts. The diversity of metabolic associations with insulin resistance highlighted metabolic signatures beyond the characteristics of metabolic syndrome (as well as beyond obesity and lipid abnormalities) and suggested a strong relation between insulin resistance and the systemic metabolite profile already evidenced in early adulthood. A combination of amino acids, lipids, and intermediates of glycolysis formed sex-specific imprints of insulin resistance on the metabolite profile that warrant attention in future physiological studies. Origins of fasting metabolite levels were also studied with dietary and physical activity data and we further tested if 12 genetic variants regulating the metabolite levels also contributed to insulin resistance. Genetic evidence did not provide support for a functional role of the metabolites in the pathogenesis of insulin resistance, yet irrespective of cause or effect, even modest insulin resistance was associated with an adverse cardiometabolic profile. Understanding the relation between insulin resistance and the systemic metabolite profile in young, normoglycemic adults may help to promote lifestyle habits for prevention of insulin resistance prior to development of hyperglycemia and overt type 2 diabetes.

P Würtz, VP Mäkinen, P Soininen, AJ Kangas, T Tukiainen, J Kettunen, MJ Savolainen, T Tammelin, JS Viikari, T Rönnemaa, M Kähönen, T Lehtimäki, S Ripatti, OT Raitakari, MR Järvelin, M Ala-Korpela Metabolic signatures of insulin resistance in 7,098 young adults Diabetes 61, 1372-80, 2012

26.3.2012 Article published in European Heart Journal
Metabolic profiling aids early cardiovascular risk assessment

Academy Prof Olli Raitakari (Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku) and Prof Mika Ala-Korpela from the Computational Medicine Team have led a novel application of quantitative serum metabolomics on the risk assessment and prediction of subclinical atherosclerosis. The study was published in the European Heart Journal.

Comprehensive metabolic profiling holds promise in cardiovascular risk assessment. In this work we showed, for the first time, that metabolic profiling, with new systemic biomarkers found, improved risk stratification for subclinical atherosclerosis over and above conventional lipids, and would be useful for early cardiovascular risk assessment. These findings indicate that serum NMR metabolomics has potential to benefit individualized treatment strategies and prevention of cardiovascular events in a very cost-effective manner.

P Würtz, JR Raiko, CG Magnussen, P Soininen, AJ Kangas, T Tynkkynen, R Thomson, R Laatikainen, MJ Savolainen, J Laurikka, P Kuukasjärvi, M Tarkka, PJ Karhunen, A Jula, JS Viikari, M Kähönen, T Lehtimäki, M Juonala, M Ala-Korpela, OT Raitakari High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis European Heart Journal 33, 2307-16, 2012

23.3.2012
Talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a talk on High-throughput serum NMR metabolomics – the new era in epidemiology & genetics in the School of Social and Community Medicine, University of Bristol, UK.

8.-9.2.2012
Plenary talk by Prof Ala-Korpela

Prof Ala-Korpela is giving a plenary talk entitled High-throughput serum NMR metabonomes – the new era of metabolic phenotyping in epidemiology & GWAS in the EGG/EAGLE Human genetics symposium in London, UK.

29.1.2012 Article published in Nature Genetics
Genome-wide association study identifies multiple loci influencing human serum metabolite levels

A novel demonstration of the fundamental importance of accurate and biochemically relevant metabolic phenotypes for genetics studies and assessing heritability has been published in Nature Genetics.

In the study we reported the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes quantified by our serum NMR metabolomics platform. We identified significant associations at 31 loci, including 11 for which there were no previous reports of associations to a metabolic trait or disorder. Analyses of 561 Finnish twin pairs suggested that the metabolic measures show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The study highlights the value of enhancing the specificity of metabolic phenotyping for genetic association analyses. The availability of 216 metabolite measures analysed by nuclear magnetic resonance provides a substantial enhancement over the measures obtained by classical clinical chemistry methods that are typically available in large population cohorts. This work forms the basis for further identification of associations providing insights into cardiometabolic disorders.

J Kettunen, T Tukiainen, AP Sarin, A Ortega-Alonso, E Tikkanen, LP Lyytikäinen, AJ Kangas, P Soininen, P Würtz, K Silander, DM Dick, RJ Rose, MJ Savolainen, J Viikari, M Kähönen, T Lehtimäki, KH Pietiläinen, M Inouye, MI McCarthy, A Jula, J Eriksson, OT Raitakari, V Salomaa, J Kaprio, MR Järvelin, L Peltonen, M Perola, NB Freimer, M Ala-Korpela, A Palotie, S Ripatti Genome-wide association study identifies multiple loci influencing human serum metabolite levels Nature Genetics 44, 269-76, 2012

2011

15.12.2011
Strategic funding for Computational Medicine

The University of Oulu has chosen Computational Medicine as one of the strategic scientific development areas of the University for 2012–2016; this strategic decision came with a grant of 850,000 € for Prof Ala-Korpela.

15.12.2011
Prof Ala-Korpela appointed in the Imperial College London

Dr Mika Ala-Korpela has been appointed a Visiting Professorship for 2012 at the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, UK.

9.12.2011 Article published in Human Molecular Genetics
Detailed metabolic and genetic characterisation reveals new associations for known lipid loci

Dr Samuli Ripatti (Institute for Molecular Medicine, Helsinki, Finland) and Prof Mika Ala-Korpela from the Computational Medicine Team have led a study that demonstrated the clear advantage of the combination of detailed genotyping and a comprehensive lipoprotein subclass profile in understanding the functions of lipid genes.

In the study we performed an association analysis of almost 100 genetic loci known to affect serum cholesterol and triglyceride levels, however the biological function and causal variants of which being mainly unknown. We reported 95 lipid loci against 216 metabolite measures, including 95 measurements on lipids and lipoprotein subclasses, obtained via our serum NMR metabolomics platform and four enzymatic lipid traits in 8,330 individuals from Finland. The genetic variation in the loci was investigated using a dense set of 440,807 directly genotyped and imputed variants around the previously identified lead SNPs. For 30 of the 95 loci, we identified new metabolic or genetic associations.

In the majority of the loci, the strongest association was to a more specific metabolite measure than the enzymatic lipids. In four loci, the smallest HDL measures showed effects opposite to the larger ones, and 14 loci had associations beyond the individual lipoprotein measures. In 27 loci, we identified SNPs with a stronger association than the previously reported markers and 12 loci harboured multiple, statistically independent variants. Our data show considerable diversity in association patterns between the loci originally identified through associations with enzymatic lipid measures and reveal association profiles of far greater detail than from routine clinical lipid measures.

This work is a clear demonstration on the importance to go beyond standard lipid measures when trying to understand the biological processes controlling lipoprotein metabolism.

T Tukiainen, J Kettunen, AJ Kangas, LP Lyytikäinen, P Soininen, AP Sarin, E Tikkanen, PF O'Reilly, MJ Savolainen, K Kaski, A Pouta, A Jula, T Lehtimäki, M Kähönen, J Viikari, MR Taskinen, M Jauhiainen, JG Eriksson, O Raitakari, V Salomaa, MR Järvelin, M Perola, A Palotie, M Ala-Korpela, S Ripatti Detailed metabolic and genetic characterization reveals new associations for 30 known lipid loci Human Molecular Genetics 21, 1444-55, 2012

16.10.2011 Article published in Nature Genetics
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Computational Medicine Research Team, as a part of an international consortium, has published in Nature Genetics a multiomics study focusing on circulating liver enzymes.

Circulating liver enzymes are widely used as indicators of liver disease. In this work we carried out a genome-wide association study in 61,089 individuals, and identified 42 independent loci associated with one or more liver markers, of which 32 were novel. To ascertain the likely candidate genes and inform biology, we used functional genomic approaches including metabolic profiling, structural genomic and gene expression analyses. We identified 69 candidate genes, including genes involved in biliary transport, glucose, carbohydrate and lipid metabolism, glycoprotein biosynthesis and cell surface glycobiology, inflammation and immunity and glutathione metabolism, as well as a number of genes of uncertain or unknown function.

This work is one of the first in which multiomics data are coherently combined to provide new insights into the genetic mechanisms and molecular pathways.

These results provide new insights into genetic mechanisms and pathways influencing markers of liver function. The serum NMR metabolomics data are in a key position in informing on the functional aspects of the genes associated with the concentrations of liver enzymes in the circulation. Prof Ala-Korpela was one of the leaders of the study.

J C Chambers, W Zhang, J Sehmi, X-Z Li, M N Wass, P Van der Harst, H Holm, S Sanna, M Kavousi, S E Baumeister, L J Coin, G-H Deng, C Gieger, N L Heard-Costa, J-J Hottenga, B Kühnel, V Kumar, V Lagou, L-M Liang, J Luan, P Marques Vidal, I Mateo Leach, P O'Reilly, J F Peden, N Rahmioglu, P Soininen, E K Speliotes, X Yuan, G Thorleifsson, B Z Alizadeh, L D Atwood, I B Borrecki, M J Brown, P Charoen, F Cucca, D Das, E J C de Geus, A L Dixon, A Döring, G Ehret, G I Eyjolfsson, M Farrall, N G Forouhi, N Friedrich, W Goessling, D F Gudbjartsson, T B Harris, A-L Hartikainen, S Heath, G M Hirchfield, A Hofman, G Homuth, E Hyppönen, H L A Janssen, T Johnson, A J Kangas, I P Kema, J P Kühn, S Lai, M Lathrop, M M Lerch, Y Li, T J Liang, J-P Lin, R J F Loos, N G Martin, M F Moffat, G W Montgomery, P Munroe, K Musunuru, Y Nakamura, C J O'Donnell, I Olafsson, B W Penninx, A Pouta, B P Prins, I Prokopenko, R Puls, A Ruokonen, M J Savolainen, D Schlessinger, J N L Schouten, U Seedorf, S Sen-Chowdhry, K A Siminovitch, J H Smit, T D Spector, W Tan, T M Teslovich, T Tukiainen, A G Uitterlinden, M M Van der Klauw, R S Vasan, C Wallace, H Wallaschofski, H-E Wichmann, G Willemsen, P Würtz, C Xu, L M Y Armstrong, AlcGen, DIAGRAM, GIANT, Global Lipids Genetics Consortium, The GOLD consortium, ICBP, MAGIC, G R Abecasis, K R Ahmadi, D I Boomsma, M Caulfield, W O Cookson, C M van Duijn, P Froguel, K Matsuda, M I McCarthy, C Meisinger, V Mooser, K H Pietiläinen, G Schumann, H Snieder, M J E Sternberg, R P Stolk, U Thorsteinsdottir, M Uda, G Waeber, N J Wareham, D M Waterworth, H Watkins, J Whitfield, J C M Witteman, B H R Wolffenbuttel, C S Fox, M Ala-Korpela, K Stefansson, P Vollenweider, H Völzke, E E Schadt, J Scott, M-R Järvelin, P Elliott, J S Kooner Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma Nature Genetics 43, 1131-8, 2011

11.9.2011 Article published in Nature
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

The International Consortium for Blood Pressure Genome-Wide Association Studies has published a genome-wide association study of systolic and diastolic blood pressure. The study was based on measurements for 200,000 individuals of European descent.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension and even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure; the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. In addition we performed analyses testing for differences in genetic effects according to body mass index (BMI) or sex, and analyses of copy number variants, pathway enrichment and metabolomics data, but we did not find any statistically significant results.

These findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

The International Consortium for Blood Pressure Genome-wide Association Studies: G B Ehret, P B Munroe, K M Rice, M Bochud, A D Johnson, D I Chasman, A V Smith, M D Tobin, G C Verwoert, S-J Hwang, V Pihur, P Vollenweider, P F O'Reilly, N Amin, J L Bragg-Gresham, A Teumer, N L Glazer, L Launer, J H Zhao, Y Aulchenko, S Heath, S Sõber, A Parsa, J Luan, P Arora, A Dehghan, F Zhang, G Lucas, A A Hicks, A U Jackson, J F Peden, T Tanaka, S H Wild, I Rudan, W Igl, Y Milaneschi, A N Parker, C Fava, J C Chambers, E R Fox, M Kumari, M J Go, P van der Harst, W H L Kao, M Sjögren, D G Vinay, M Alexander, Y Tabara, S Shaw-Hawkins, P H Whincup, Y Liu, G Shi, J Kuusisto, B Tayo, M Seielstad, X Sim, K-D H Nguyen, T Lehtimäki, G Matullo, Y Wu, T R Gaunt, N C Onland-Moret, M N Cooper, C G P Platou, E Org, R Hardy, S Dahgam, J Palmen, V Vitart, P S Braund, T Kuznetsova, C S P M Uiterwaal, A Adeyemo, W Palmas, H Campbell, B Ludwig, M Tomaszewski, I Tzoulaki, N D Palmer, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, T Aspelund, M Garcia, Y-P C Chang, J R O'Connell, N I Steinle, D E Grobbee, D E Arking, S L Kardia, A C Morrison, D Hernandez, S Najjar, W L McArdle, D Hadley, M J Brown, J M Connell, A D Hingorani, I N M Day, D A Lawlor, J P Beilby, R W Lawrence, R Clarke, J C Hopewell, H Ongen, A W Dreisbach, Y Li, J H Young, J C Bis, M Kähönen, J Viikari, L S Adair, N R Lee, M-H Chen, M Olden, C Pattaro, J A H Bolton, A Kâšâttgen, S Bergmann, V Mooser, N Chaturvedi, T M Frayling, M Islam, T H Jafar, J Erdmann, S R Kulkarni, S R Bornstein, J Grässler, L Groop, B F Voight, J Kettunen, P Howard, A Taylor, S Guarrera, F Ricceri, V Emilsson, A Plump, I Barroso, K-T Khaw, A B Weder, S C Hunt, Y V Sun, R N Bergman, F S Collins, L L Bonnycastle, L J Scott, H M Stringham, L Peltonen, M Perola, E Vartiainen, S-M Brand, J A Staessen, T J Wang, P R Burton, M S Artigas, Y Dong, H Snieder, X Wang, H Zhu, K K Lohman, M E Rudock, S R Heckbert, N L Smith, K L Wiggins, A Doumatey, D Shriner, G Veldre, M Viigimaa, S Kinra, D Prabhakaran, V Tripathy, C D Langefeld, A Rosengren, D S Thelle, A M Corsi, A Singleton, T Forrester, G Hilton, C A McKenzie, T Salako, N Iwai, Y Kita, T Ogihara, T Ohkubo, T Okamura, H Ueshima, S Umemura, S Eyheramendy, T Meitinger, H-E Wichmann, Y S Cho, H-L Kim, J-Y Lee, J Scott, J S Sehmi, W Zhang, B Hedblad, P Nilsson, G D Smith, A Wong, N Narisu, A Stančáková, L J Raffel, J Yao, S Kathiresan, C O'Donnell, S M Schwartz, M A Ikram, W T Longstreth Jr, T H Mosley, S Seshadri, N R G Shrine, L V Wain, M A Morken, A J Swift, J Laitinen, I Prokopenko, P Zitting, J A Cooper, S E Humphries, J Danesh, A Rasheed, A Goel, A Hamsten, H Watkins, S J L Bakker, W H van Gilst, C S Janipalli, K R Mani, C S Yajnik, A Hofman, F US Mattace-Raso, B A Oostra, A Demirkan, A Isaacs, F Rivadeneira, E G Lakatta, M Orru, A Scuteri, M Ala-Korpela, A J Kangas, L-P Lyytikäinen, P Soininen, T Tukiainen, P Würtz, R T-H Ong, M Dörr, H K Kroemer, U Völker, H Völzke, P Galan, S Hercberg, M Lathrop, D Zelenika, P Deloukas, M Mangino, T D Spector, G Zhai, J F Meschia, M A Nalls, P Sharma, J Terzic, M J K Kumar, M Denniff, E Zukowska-Szczechowska, L E Wagenknecht, F G R Fowkes, F J Charchar, P E H Schwarz, C Hayward, X Guo, C Rotimi, M L Bots, E Brand, N J Samani, O Polasek, P J Talmud, F Nyberg, D Kuh, M Laan, K Hveem, L J Palmer, Y T van der Schouw, J P Casas, K L Mohlke, P Vineis, O Raitakari, S K Ganesh, T Y Wong, E S Tai, R S Cooper, M Laakso, D C Rao, T B Harris, R W Morris, A F Dominiczak, M Kivimaki, M G Marmot, T Miki, D Saleheen, G R Chandak, J Coresh, G Navis, V Salomaa, B-G Han, X Zhu, J S Kooner, O Melander, P M Ridker, S Bandinelli, U B Gyllensten, A F Wright, J F Wilson, L Ferrucci, M Farrall, J Tuomilehto, P P Pramstaller, R Elosua, N Soranzo, E J G Sijbrands, D Altshuler, R J F Loos, A R Shuldiner, C Gieger, P Meneton, A G Uitterlinden, N J Wareham, V Gudnason, J I Rotter, R Rettig, M Uda, D P Strachan, J C M Witteman, A-L Hartikainen, J S Beckmann, E Boerwinkle, R S Vasan, M Boehnke, M G Larson, M-R Järvelin, B M Psaty, G R Abecasis, A Chakravarti, P Elliott, C M van Duijn, C Newton-Cheh, D Levy, M J Caulfield, T Johnson Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk Nature 478, 103-9, 2011

8.-10.6.2011
Invited talk by Dr Soininen

Dr Soininen is giving an invited talk entitled Two years of high-throughput serum NMR metabonomics in the 33rd Finnish NMR symposium, Jyväskylä, Finland.

16.05.2011
Academy of Finland funding for Dr Würtz

Academy of Finland has awarded Dr Würtz 277,700 EUR for a 3-year postdoctoral research project entitled Metabolic profiling of atherosclerosis – from subclinical disease to cardiovascular endpoints.

2010

21.12.2010 Article published in Molecylar Systems Biology
Metabonomic, transcriptomic, and genomic variation of a population cohort

The first human study in which three different omics data sets are combined for the same individuals in a population based setting has been published in Molecular Systems Biology.

The study assesses metabonomic, transcriptomic, and genomic variation for a large population-based cohort from the capital region of Finland. Network analyses identified a set of highly correlated genes, the lipid­leukocyte (LL) module, as having a prominent role in over 80 serum metabolites (of 134 measures quantified), including lipoprotein subclasses, lipids, and amino acids. Concurrent association with immune response markers suggested the LL module as a possible link between inflammation, metabolism, and adiposity. Further, genomic variation was used to generate a directed network and infer the LL module's largely reactive nature to metabolites.

For example, gene co-expression in circulating leukocytes was shown to be dependent on serum metabolite concentrations, providing evidence for the hypothesis that molecular networks themselves are conditional on environmental factors. These findings show the importance and opportunity of systematic molecular investigation of human population samples

M Inouye, J Kettunen, P Soininen, K Silander, S Ripatti, L S Kumpula, A Jula, J Leiviskä, E Hämäläinen, P Jousilahti, A J Kangas, S Männistö, M J Savolainen, A Jula, J Leiviskä, A Palotie, V Salomaa, M Perola, M Ala-Korpela, L Peltonen Metabonomic, transcriptomic, and genomic variation of a population cohort Molecular Systems Biology 6, 441, 2010

17.9.2010
Academy of Finland funding for Dr Soininen

Academy of Finland has awarded Dr Soininen 272,000 EUR for postdoctoral’s research project entitled High-Throughput Serum NMR Metabonomics in Common Vascular Diseases - Combination with Extensive Clinical Studies Including Genetic Data.

1.8.2010
Prof Ala-Korpela appointed in China

Dr Mika Ala-Korpela has been appointed a 3-year Visiting Professorship in Omics Sciences at the College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan Province, China.

22.4.2010
Sydäntutkimussäätiö rahoittaa vaskulaaritautien metabonomiikkatutkimusta

Sydäntutkimussäätiön hallitus on 22.4.2010 pidetyssä kokouksessa myöntänyt 30.000 euron apurahan prof Mika Ala-Korpelan ja prof Markku J. Savolaisen yhdessä johtamaan tutkimukseen: Geneettisen ja metabolisen tiedon yhdistäminen vaskulaaritautien varhaisdiagnostiikassa. Apuraha liittyy laskennallisen lääketieteen tutkimusryhmässä käynnissä olevaan tutkimusyhteistyöhön.

Tutkimuksen tavoitteena on geneettisen ja metabolisen informaation yhdistäminen molekylaaristen tautiprosessien ymmärtämiseksi ja riskien ennustamiseksi. Uskomme vahvasti monitieteisen ja holistisen näkökulman hyödyttävän erityisesti multigeenisten kansantautien tapauksessa, missä terveyden ja sairauden raja on mm. tautitilojen hitaan ajallisen kehittymisen vuoksi erittäin vaikeasti määriteltävissä. Massiivisten datajoukkojen ja uusien menetelmien uskotaan auttavan ymmärtämään yleisten tautien molekulaarista etiologiaa, riskin arviointia, ennaltaehkäisyä, diagnostiikkaa ja hoitoa. Selkeä tavoitteemme on parantaa vaskulaaritautien riskin ennustamista siten, että voitaisiin saavuttaa yhteiskunnan terveydenhuollon kustannussäästöjä ja samalla yksilöiden parempaa terveyden ylläpitoa sekä minimoida tauteihin liittyvien komplikaatioiden aiheuttamia ongelmia ja inhimillistä kärsimystä.

13.4.2010
Diabetestutkimussäätiö rahoittaa tyypin 2 diabeteksen metabonomiikkatutkimusta

2009

5.9.2009 Article published in Journal of Lipid Research
Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps

The Computational Medicine Research Team has published an application of self-organizing maps to the combination of concentration and compositional lipoprotein data. The application, published in the Journal of Lipid Research, was shown to enable data-driven lipoprotein phenotyping beyond the experimentally available classifications.

The study illustrates five different lipoprotein phenotypes, all with characteristic plasma concentration profiles as well as distinct compositional features. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. Thus, deeper insight into the compositional variations in the lipoprotein particles appears a fundamental issue.


The application of self-organizing maps to the combination of concentration and compositional lipoprotein data enabled data-driven lipoprotein phenotyping beyond the experimentally available classifications. Five different phenotypes are illustrated, all with characteristic plasma concentration profiles as well as distinct compositional features. In particular, deeper insight into the compositional variations in the lipoprotein particles appears a fundamental issue.

L S Kumpula, S M Mäkelä, V-P Mäkinen, A Karjalainen, J M Liinamaa, K Kaski, M J Savolainen, M L Hannuksela, M Ala-Korpela Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps Journal of Lipid Research 51, 431-9, 2010

30.7.2009 Article published in Analyst
High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism

The Computational Medicine Research Team has established, optimised, and tested a new protocol for the high-throughput NMR metabolomics of serum.

To the best of our knowledge, the presented set-up is unique in the sense of experimental high-throughput, cost-effectiveness, and automated multi-metabolic data analyses. We also demonstrated in a real epidemiological study with 4,407 samples, that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome. The high-throughput of up to 50,000 serum samples per year is also paving the way for this technology in large-scale clinical and epidemiological studies. In contradiction to single Œbiomarkers¹, the application of this holistic NMR approach and the integrated computational methods provides a data-driven systems biology approach to biomedical research.

This work has become highly sited and the serum NMR metabolomics platform, developed on the basis of this work, is becoming worldwide applied in epidemiology and genetics.

P Soininen, A J Kangas, P Würtz, T Tukiainen, T Tynkkynen, R Laatikainen, M-R Järvelin, M Kähönen, T Lehtimäki, J Viikari, O T Raitakari, M J Savolainen, M Ala-Korpela High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism Analyst 134, 1781-5, 2009

9.3.2009 Article published in Annals of Medicine
A new computational extended Friedewald approach: ApoB and IDL, but not LDL, are associated with mortality in type 1 diabetes

The Computational Medicine Research Team has developed a new computational approach which allows estimation of a clinically useful lipoprotein profile - including VLDL-TG, IDL-C, LDL-C, HDL2-C, apoA-I, and apoB - with no additional costs if the conventional Friedewald inputs are available.

In the study the validity and biological significance of the artificial neural network regression models was demonstrated in a realistic clinical situation for a large set of patients with type 1 diabetes. The relations of various lipoprotein lipid and apolipoprotein (apo) measures on the Friedewald inputs, i.e. plasma triglycerides (TG), cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were studied.

The new approach is expected to be valuable in assessing the separate importance of IDL-C and LDL-C, as well as the other lipoprotein measures, as risk factors for macrovascular complications, an issue inherently hampered when using the traditional Friedewald formula. The new approach is freely accessible via an online service at http://www.computationalmedicine.fi/software/Lipido.

J Niemi, VP Mäkinen, J Heikkonen, L Tenkanen, Y Hiltunen, ML Hannuksela, M Jauhiainen, C Forsblom, MR Taskinen, YA Kesäniemi, MJ Savolainen, K Kaski, PH Groop, PT Kovanen, M Ala-Korpela Estimation of VLDL, IDL, LDL, HDL2, apoA-I, and apoB from the Friedewald inputs--apoB and IDL, but not LDL, are associated with mortality in type 1 diabetes Annals of Medicine 41, 451-61, 2009

1.3.2009
FT Mika Ala-Korpela nimitetty laskennallisen lääketieteen professoriksi

Dosentti, FT Mika Ala-Korpela on 1. maaliskuuta 2009 alkaen nimitetty laskennallisen lääketieteen professoriksi Oulun yliopiston lääketieteellisessä tiedekunnassa, kliinisen lääketieteen laitoksella. Professuuri on yksi ensimmäisistä maailmassa tällä uudella tieteenalalla.

Laskennallinen lääketiede yhdistää ja kehittää matematiikan, biokemian ja laskennallisen tekniikan ja tieteen menetelmiä ja monitieteisiä lähestymistapoja eri tautien kvantitatiiviseen ja molekylaariseen ymmärtämiseen, riskianalyysiin ja diagnostiikkaan. Keskeisenä osatekijänä on systeemibiologinen näkemys ihmisen toiminnasta ja tämän kompleksisuuden käsittelyyn soveltuvat uudet kokeelliset ja laskennalliset menetelmät. Yhteiskunnallisena tavoitteena on sosioekonomisten lähestymistapojen integrointi tautien riskianalytiikkaan ja hoidon suunnitteluun; näin on mahdollista saada merkittäviä säästöjä terveydenhuollossa ja samalla ennalta ehkäistä yksilötasolla kärsimystä tuovien tautien eteneminen ja tautitapahtumat.

2008

28.10.2008
Metabonomiikkatutkimukseen rahoitusta Suomen Akatemiasta

Laskennallisen lääketieteen ryhmälle on myönnetty Suomen Akatemiasta, kansanterveyden haasteet -tutkimusohjelmasta (SALVE) tutkimusrahoitusta yhteistyössä Prof Markku Savolaisen johtaman tutkimusryhmän kanssa (Oulun yliopisto). Tutkimus keskittyy uusien menetelmien kehittämiseen metabolisten riskien havaitsemiseen ja hoitamiseen.

Prof Mika Ala-Korpelan johtama osaprojekti "1H NMR -metabonomiikka - molekylaarinen menetelmä henkilökohtaisen tautiriskin arvioimiseksi" keskittyy ko. uuden metodologian kehittämiseen ja soveltamiseen vaskulaaristen kansantautien riskien arviointiin.

Biotieteissä genetiikan näkökulma on perinteisesti korostunut. Genetiikan voima tulee kuitenkin parhaiten esiin niissä harvinaisissa tapauksissa, joissa yksittäiset geenivirheet kontrolloivat tautiprosessia. Genetiikan yleinen käytännöllinen sovellettavuus on kuitenkin varsin rajallista tapauksissa, joissa tautin etiologia on useiden geenien säätelemää. Näin on kaikissa kansantaudeissa, kuten diabeteksessa ja sydän- ja verisuonitaudeissa. Yleisesti, niin fysiologisen normaalitilan kuin erilaisten tautitilojenkin metabolinen fenotyyppi on vaikeasti määriteltävissä. Näistä voidaan kuitenkin saada hyvä yleiskuva tarkastelemalla systeemistä metaboliaa ja metabolisia profiileita, esim. veren seerumissa. Yhdeksi biotieteiden merkittävistä sovelluskentistä onkin viime aikoina noussut metabonomiikka; ihmisen kehon nesteiden 1H NMR -spektroskopia on yksi keskeisimpiä alueen tutkimuskohteista.

Tässä yhteistyössä on tarkoitus tehdä laajaa kliinistä ja biokemiallista yhteistyötä ja pyrkiä tautitilojen riskin kokonaisvaltaiseen arviointiin ja ymmärtämiseen systeemibiologisesta näkökulmasta. Seerumin monipuolisten metabolisten profiilien, mukaanlukien lipoproteiinien alaluokat, määrittäminen 1H NMR -spektroskopialla on yhteistyössä keskeisessä roolissa. Yhtenä keskeisenä tavoitteena on geneettisen ja metabolisen informaation yhdistäminen molekylaaristen tautiprosessien ymmärtämiseksi ja riskien ennustamiseksi.

Uskomme tällaisen monitieteisen ja holistisen näkökulman hyödyttävän erityisesti multigeenisten kansantautien tapauksessa, missä terveyden ja sairauden raja on erittäin vaikeasti määriteltävissä. Selkeä tavoitteemme on parantaa vaskulaaritautien riskin ennustamista siten, että voitaisiin saavuttaa yhteiskunnan terveyden huollon kustannussäästöjä ja samalla yksilöiden parempaa terveyden ylläpitoa ja tauteihin liittyvien ongelmien ja tuskan minimointia. Uskomme tähän päästävän terveyttä ylläpitävillä menetelmillä ja riittävän aikaisella puuttumisella metabolisiin ongelmiin – ei perinteisesti sairauksia hoitamalla.

20.6.2008 Article published in Chemistry and Physics of Lipids
Reconsideration of hydrophobic lipid distributions in lipoprotein particles

The Computational Medicine Research Team has published a new structural model for lipoprotein particles.

Lipoprotein particles are commonly known as micellar aggregates with hydrophobic lipids located within the core and amphipathic molecules in the surface. Using a new structural model for optimizing the distribution of hydrophobic lipids, namely triglyceride (TG) and cholesterol ester (CE) molecules, we reveal that particle size-dependent proportion of these Œcore lipids¹ may locate in the surface of lipoprotein particles. The composition of the particles also strongly influences the actual molecular content of the surface. These structural models provide an intuitive and coherent structural rationale for various metabolic cascades in lipoprotein metabolism with the catalytic enzyme action and molecular binding for transport proteins taking place at the surface of the particles.


Schematic cross-sectional molecular models of VLDL2, IDL, LDL2, HDL2b and HDL3c particles with the optimized distribution of TG and CE between the core and surface. The molecular compositions are from 12 individuals with these particles isolated using ultracentrifugation. The penetration of TG and CE into the particle surface occurs mainly via loosely packed phosphatidylcholine (PC)-rich, free cholesterol (FC)-poor domains (a–e). Note also the tendency of cholesterol rings to interact (a); CE penetration (b, c, e) and TG penetration with fatty acid chains ahead (a–e); a kinked TG (d) and a kinked CE molecule in the surface (e); the nanodomains consisting of mainly sphingomyelin (SM) and FC are tightly packed and impede the penetration of TG and CE into the surface (f).

LS Kumpula, JM Kumpula, MR Taskinen, M Jauhiainen, K Kaski, M Ala-Korpela Reconsideration of hydrophobic lipid distributions in lipoprotein particles Chemistry and Physics of Lipids 155, 57-62, 2008

12.2.2008 Article published in Molecular Systems Biology
1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death

The Computational Medicine Research Team has developed a new metabonomics framework to visualize and interpret the data and to link the metabolic profiles to the underlying diagnostic and biochemical variables. The results indicate complex interactions between diabetic kidney disease, insulin resistance and the metabolic syndrome. We illustrate how a single 1H NMR protocol is able to identify the polydiagnostic metabolite manifold of type I diabetes and how its alterations translate to clinical phenotypes, clustering of micro- and macrovascular complications, and mortality during several years of follow-up. This work demonstrates the diffuse nature of complex vascular diseases and the limitations of single diagnostic biomarkers. However, it also promises cost-effective solutions through high-throughput analytics and advanced computational methods, as applied here in a case that is representative of the real clinical situation.

This work demonstrated the benefits of integrating modern biochemical analytics with computer-assisted knowledge discovery. This work has become highly sited and can be seen as a forerunner of metabolomics-based individual risk assessment of complex multi-factorial diseases.

VP Mäkinen, P Soininen, C Forsblom, M Parkkonen, P Ingman, K Kaski, PH Groop, , M Ala-Korpela 1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death Molecular Systems Biology 4, 167, 2008