About the Authors

Ida Surakka

Contributed equally to this work with: Ida Surakka, Aaron Isaacs

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

Aaron Isaacs

Contributed equally to this work with: Ida Surakka, Aaron Isaacs

Affiliations Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Leiden, The Netherlands

Lennart C. Karssen

Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

Pirkka-Pekka P. Laurila

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

Rita P. S. Middelberg

Affiliations Queensland Institute of Medical Research, Brisbane, Australia, Department of Medicine, Prince Charles Hospital, Chermside, Australia

Emmi Tikkanen

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

Janina S. Ried

Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

Claudia Lamina

Affiliation Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

Massimo Mangino

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

Wilmar Igl

Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

Jouke-Jan Hottenga

Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

Vasiliki Lagou

Affiliations Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

Pim van der Harst

Affiliation Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Irene Mateo Leach

Affiliation Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Tõnu Esko

Affiliations The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia, The Institute of Molecular and Cellular Biology of the University of Tartu, Tartu, Estonia

Zoltán Kutalik

Affiliations Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, Swiss Institute of Bioinformatics, Lausanne, Switzerland

Nicholas W. Wainwright

Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

Maksim V. Struchalin

Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

Antti-Pekka Sarin

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

Antti J. Kangas

Affiliation Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland

Jorma S. Viikari

Affiliation Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland

Markus Perola

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia

Taina Rantanen

Affiliation Department of Health Sciences, Gerontology Research Centre, University of Jyväskylä, Jyväskylä, Finland

Ann-Kristin Petersen

Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

Pasi Soininen

Affiliation NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland

Åsa Johansson

Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

Nicole Soranzo

Affiliations Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

Andrew C. Heath

Affiliation Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America

Theodore Papamarkou

Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

Inga Prokopenko

Affiliations Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

Anke Tönjes

Affiliations Medical Department, University of Leipzig, Leipzig, Germany, IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany

Florian Kronenberg

Affiliation Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

Angela Döring

Affiliations Institute of Epidemiology I, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

Fernando Rivadeneira

Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

Grant W. Montgomery

Affiliation Queensland Institute of Medical Research, Brisbane, Australia

John B. Whitfield

Affiliation Queensland Institute of Medical Research, Brisbane, Australia

Mika Kähönen

Affiliations Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland, Medical School, University of Tampere, Tampere, Finland

Terho Lehtimäki

Affiliations Medical School, University of Tampere, Tampere, Finland, Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland

Nelson B. Freimer

Affiliations Department of Psychiatry, University of California Los Angeles, Los Angeles, United States of America, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, United States of America

Gonneke Willemsen

Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

Eco J. C. de Geus

Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

Aarno Palotie

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America

Manj S. Sandhu

Affiliations Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom, Non-Communicable Disease Research Group, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

Dawn M. Waterworth

Affiliation Genetics, Medicines Discovery, and Development, GlaxoSmithKline, Philadelphia, Pennsylvania, United States of America

Andres Metspalu

Affiliations The Estonian Genome Center and the Center of Translational Genomics of the University of Tartu, Tartu, Estonia, The Institute of Molecular and Cellular Biology of the University of Tartu, Tartu, Estonia, The Estonian Biocentre, Tartu, Estonia

Michael Stumvoll

Affiliation Department of Medicine, University of Leipzig, Leipzig, Germany

André G. Uitterlinden

Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

Antti Jula

Affiliation Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland

Gerjan Navis

Affiliation Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Cisca Wijmenga

Affiliation Department of Genetics, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands

Bruce H. R. Wolffenbuttel

Affiliation Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Marja-Riitta Taskinen

Affiliation Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Mika Ala-Korpela

Affiliations Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland, NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland, Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, University of Oulu, Oulu, Finland

Jaakko Kaprio

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Department of Public Health, University of Helsinki, Helsinki, Finland, Unit for Child and Adolescent Mental Health, National Institute for Health and Welfare, Helsinki, Finland

Kirsten O. Kyvik

Affiliations Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark, Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark

Dorret I. Boomsma

Affiliation Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

Nancy L. Pedersen

Affiliation Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Ulf Gyllensten

Affiliation Department of Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden

James F. Wilson

Affiliation Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom

Igor Rudan

Affiliations Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom, Croatian Centre for Global Health, University of Split Medical School, Split, Croatia

Harry Campbell

Affiliation Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom

Peter P. Pramstaller

Affiliations Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, Affiliated Institute of the University of Lübeck, Lübeck, Germany, Department of Neurology, University of Lübeck, Lübeck, Germany, Department of Neurology, Central Hospital of Bolzano, Bolzano, Italy

Tim D. Spector

Affiliation Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

Jacqueline C. M. Witteman

Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

Johan G. Eriksson

Affiliations Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, Folkhälsan Research Centre, Helsinki, Finland, Vasa Central Hospital, Vasa, Finland, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

Veikko Salomaa

Affiliation Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland

Ben A. Oostra

Affiliation Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

Olli T. Raitakari

Affiliations Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Clinical Physiology, University of Turku and Turku University Hospital, Turku, Finland

H.-Erich Wichmann

Affiliations Institute of Epidemiology I, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany, Klinikum Grosshadern, Munich, Germany

Christian Gieger

Affiliation Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

Marjo-Riitta Järvelin

Affiliation Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom

Nicholas G. Martin

Affiliation Queensland Institute of Medical Research, Brisbane, Australia

Albert Hofman

Affiliations Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

Mark I. McCarthy

Affiliations Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom

Leena Peltonen

† Deceased.

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland, Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland, The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America

Cornelia M. van Duijn

Affiliations Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Leiden, The Netherlands, Netherlands Genomics Initiative (NGI)–sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands

Yurii S. Aulchenko

These authors also contributed equally to this work.

Affiliation Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

Samuli Ripatti

samuli.ripatti@fimm.fi

These authors also contributed equally to this work.

Affiliations Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland, Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

for the ENGAGE Consortium

Competing Interests

One of the replication cohorts used in the study is partially funded by GlaxoSmithKline.

Author Contributions

† Deceased.

Conceived and designed the experiments: LP CMD YSA SR. Performed the experiments: IS AI LCK. Analyzed the data: IS AI LCK PPL RPSM ET JSR CL MM WI JJH VL PH IML TE ZK NWW MVS APS AJK. Contributed reagents/materials/analysis tools: JSV MP TR AKP PS ÅJ NS ACH TP IP AT FK AD FR GWM JBW MK TL NBF GW EJCG AP MSS DW AM MS AGU AJ GN CW BHRW MRT MAK JK KOK DIB NLP UG JFW IR HC PPP TDS JCMW JGE VS BAO OTR HEW CG MRJ NGM AH. Wrote the paper: IS AI MIM CMD YSA SR.