Advertisement
Research Article

The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

  • Tove Fall equal contributor,

    equal contributor Contributed equally to this work with: Tove Fall, Sara Hägg, Reedik Mägi

    Affiliations: Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    X
  • Sara Hägg equal contributor,

    equal contributor Contributed equally to this work with: Tove Fall, Sara Hägg, Reedik Mägi

    Affiliations: Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    X
  • Reedik Mägi equal contributor,

    equal contributor Contributed equally to this work with: Tove Fall, Sara Hägg, Reedik Mägi

    Affiliations: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Estonian Genome Center, University of Tartu, Tartu, Estonia

    X
  • Alexander Ploner,

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

    X
  • Krista Fischer,

    Affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia

    X
  • Momoko Horikoshi,

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

    X
  • Antti-Pekka Sarin,

    Affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    X
  • Gudmar Thorleifsson,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

    X
  • Claes Ladenvall,

    Affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University and Skåne University Hospital, Malmö, Sweden

    X
  • Mart Kals,

    Affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia

    X
  • Maris Kuningas,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Harmen H. M. Draisma,

    Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands

    X
  • Janina S. Ried,

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

    X
  • Natalie R. van Zuydam,

    Affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

    X
  • Ville Huikari,

    Affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland

    X
  • Massimo Mangino,

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

    X
  • Emily Sonestedt,

    Affiliation: Diabetes and Cardiovascular Diseases Genetic Epidemiology Research Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden

    X
  • Beben Benyamin,

    Affiliations: Queensland Institute of Medical Research, Herston, Australia, Queensland Brain Institute, University of Queensland, St Lucia, Australia

    X
  • Christopher P. Nelson,

    Affiliations: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom, National Institute for Health Research, Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom

    X
  • Natalia V. Rivera,

    Affiliations: IRCSS Multimedica, Milan, Italy, Institute of Genetics and Biomedical Research, Consiglio Nazionale delle Ricerche, Milan, Italy, Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Kati Kristiansson,

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

    X
  • Huei-yi Shen,

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

    X
  • Aki S. Havulinna,

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

    X
  • Abbas Dehghan,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands

    X
  • Louise A. Donnelly,

    Affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

    X
  • Marika Kaakinen,

    Affiliations: Institute of Health Sciences, University of Oulu, Oulu, Finland, Biocenter Oulu, University of Oulu, Oulu, Finland

    X
  • Marja-Liisa Nuotio,

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

    X
  • Neil Robertson,

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

    X
  • Renée F. A. G. de Bruijn,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • M. Arfan Ikram,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Najaf Amin,

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

    X
  • Anthony J. Balmforth,

    Affiliation: Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, School of Medicine, University of Leeds, Leeds, United Kingdom

    X
  • Peter S. Braund,

    Affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom

    X
  • Alexander S. F. Doney,

    Affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

    X
  • 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

    X
  • Paul Elliott,

    Affiliation: MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom

    X
  • Tõnu Esko,

    Affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia

    X
  • Oscar H. Franco,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands

    X
  • Solveig Gretarsdottir,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

    X
  • Anna-Liisa Hartikainen,

    Affiliation: Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, University of Oulu, Oulu, Finland

    X
  • Kauko Heikkilä,

    Affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland

    X
  • Karl-Heinz Herzig,

    Affiliations: Biocenter Oulu, University of Oulu, Oulu, Finland, Institute of Biomedicine, University of Oulu, Oulu, Finland, Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland

    X
  • Hilma Holm,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

    X
  • Jouke Jan Hottenga,

    Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands

    X
  • Elina Hyppönen,

    Affiliation: Centre for Paediatric Epidemiology and Biostatistics and Medical Research Council Centre for the Epidemiology of Child Health, University College London Institute of Child Health, London, United Kingdom

    X
  • Thomas Illig,

    Affiliations: Hannover Unified Biobank, Hannover Medical School, Hannover, Germany, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

    X
  • Aaron Isaacs,

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

    X
  • Bo Isomaa,

    Affiliations: Department of Social Services and Health Care, Jakobstad, Finland, Folkhälsan Research Centre, Helsinki, Finland

    X
  • Lennart C. Karssen,

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

    X
  • Johannes Kettunen,

    Affiliations: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    X
  • Wolfgang Koenig,

    Affiliation: Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Ulm, Germany

    X
  • Kari Kuulasmaa,

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

    X
  • Tiina Laatikainen,

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

    X
  • Jaana Laitinen,

    Affiliation: Finnish Institute of Occupational Health, Helsinki, Finland

    X
  • Cecilia Lindgren,

    Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

    X
  • Valeriya Lyssenko,

    Affiliations: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University and Skåne University Hospital, Malmö, Sweden, Steno Diabetes Center, Gentofte, Denmark

    X
  • Esa Läärä,

    Affiliation: Department of Mathematical Sciences, University of Oulu, Oulu, Finland

    X
  • Nigel W. Rayner,

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

    X
  • Satu Männistö,

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

    X
  • Anneli Pouta,

    Affiliations: Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, University of Oulu, Oulu, Finland, Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland

    X
  • Wolfgang Rathmann,

    Affiliation: Institute of Biometrics and Epidemiology, German Diabetes Center, Düsseldorf University, Düsseldorf, Germany

    X
  • Fernando Rivadeneira,

    Affiliations: Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Aimo Ruokonen,

    Affiliation: Institute of Diagnostics, University of Oulu, Oulu, Finland

    X
  • Markku J. Savolainen,

    Affiliations: Biocenter Oulu, University of Oulu, Oulu, Finland, Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, Oulu, Finland

    X
  • Eric J. G. Sijbrands,

    Affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Kerrin S. Small,

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

    X
  • Jan H. Smit,

    Affiliations: The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands, Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

    X
  • Valgerdur Steinthorsdottir,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

    X
  • Ann-Christine Syvänen,

    Affiliation: Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    X
  • Anja Taanila,

    Affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland

    X
  • Martin D. Tobin,

    Affiliation: Department of Health Sciences, University of Leicester, Leicester, United Kingdom

    X
  • Andre G. Uitterlinden,

    Affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Sara M. Willems,

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

    X
  • Gonneke Willemsen,

    Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands

    X
  • Jacqueline Witteman,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands

    X
  • Markus Perola,

    Affiliations: Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    X
  • Alun Evans,

    Affiliation: Centre for Public Health, Queen's University of Belfast, Belfast, Northern Ireland

    X
  • Jean Ferrières,

    Affiliation: Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France

    X
  • Jarmo Virtamo,

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

    X
  • Frank Kee,

    Affiliation: Centre of Excellence for Public Health Northern Ireland, Queen's University of Belfast, Belfast, Northern Ireland

    X
  • David-Alexandre Tregouet,

    Affiliation: Institute of Cardiometabolism and Nutrition, INSERM UMR S937, Pierre and Marie Curie University, Paris, France

    X
  • Dominique Arveiler,

    Affiliation: Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France

    X
  • Philippe Amouyel,

    Affiliation: Institut Pasteur de Lille, INSERM U744, Université Lille Nord de France, Lille, France

    X
  • Marco M. Ferrario,

    Affiliation: Epidemiology and Preventive Medicine Research Centre, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy

    X
  • Paolo Brambilla,

    Affiliation: Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy

    X
  • Alistair S. Hall,

    Affiliation: Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, School of Medicine, University of Leeds, Leeds, United Kingdom

    X
  • Andrew C. Heath,

    Affiliation: Washington University School of Medicine, St Louis, Missouri, United States of America

    X
  • Pamela A. F. Madden,

    Affiliation: Washington University School of Medicine, St Louis, Missouri, United States of America

    X
  • Nicholas G. Martin,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

    X
  • Grant W. Montgomery,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

    X
  • John B. Whitfield,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

    X
  • Antti Jula,

    Affiliation: Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland

    X
  • Paul Knekt,

    Affiliation: Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki, Finland

    X
  • Ben Oostra,

    Affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

    X
  • Cornelia M. van Duijn,

    Affiliations: Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Genomic Initiative, Leiden, The Netherlands, Centre for Medical Systems Biology, Leiden, The Netherlands

    X
  • Brenda W. J. H. Penninx,

    Affiliations: The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

    X
  • George Davey Smith,

    Affiliation: MRC Centre for Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom

    X
  • Jaakko Kaprio,

    Affiliations: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland, Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland

    X
  • Nilesh J. Samani,

    Affiliations: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom, National Institute for Health Research, Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom

    X
  • Christian Gieger,

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

    X
  • Annette Peters,

    Affiliations: Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Munich Heart Alliance, Munich, Germany

    X
  • 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

    X
  • Dorret I. Boomsma,

    Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands

    X
  • Eco J. C. de Geus,

    Affiliations: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands

    X
  • TiinaMaija Tuomi,

    Affiliations: Folkhälsan Research Centre, Helsinki, Finland, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

    X
  • Chris Power,

    Affiliation: Centre for Paediatric Epidemiology and Biostatistics and Medical Research Council Centre for the Epidemiology of Child Health, University College London Institute of Child Health, London, United Kingdom

    X
  • Christopher J. Hammond,

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

    X
  • Tim D. Spector,

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

    X
  • Lars Lind,

    Affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    X
  • Marju Orho-Melander,

    Affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University and Skåne University Hospital, Malmö, Sweden

    X
  • Colin Neil Alexander Palmer,

    Affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

    X
  • Andrew D. Morris,

    Affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

    X
  • Leif Groop,

    Affiliations: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University and Skåne University Hospital, Malmö, Sweden

    X
  • Marjo-Riitta Järvelin,

    Affiliations: Institute of Health Sciences, University of Oulu, Oulu, Finland, Biocenter Oulu, University of Oulu, Oulu, Finland, Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom

    X
  • Veikko Salomaa,

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

    X
  • Erkki Vartiainen,

    Affiliation: Division of Welfare and Health Promotion, National Institute for Health and Welfare, Helsinki, Finland

    X
  • Albert Hofman,

    Affiliations: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands

    X
  • Samuli Ripatti,

    Affiliations: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

    X
  • Andres Metspalu,

    Affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia

    X
  • Unnur Thorsteinsdottir,

    Affiliations: deCODE Genetics, Reykjavik, Iceland, Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    X
  • Kari Stefansson,

    Affiliations: deCODE Genetics, Reykjavik, Iceland, Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    X
  • Nancy L. Pedersen ,

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

    These authors are joint senior authors on this work.

    X
  • Mark I. McCarthy ,

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

    These authors are joint senior authors on this work.

    X
  • Erik Ingelsson mail,

    erik.ingelsson@medsci.uu.se (EI); i.prokopenko@imperial.ac.uk (IP)

    Affiliations: Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

    These authors are joint senior authors on this work.

    X
  • Inga Prokopenko mail,

    erik.ingelsson@medsci.uu.se (EI); i.prokopenko@imperial.ac.uk (IP)

    Affiliations: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom, Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom

    These authors are joint senior authors on this work.

    X
  • for the European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium
  • Published: June 25, 2013
  • DOI: 10.1371/journal.pmed.1001474
  • Featured in PLOS Collections

About the Authors

Tove Fall, Sara Hägg, Erik Ingelsson
Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Tove Fall, Sara Hägg, Alexander Ploner, Nancy L. Pedersen, Erik Ingelsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Reedik Mägi, Momoko Horikoshi, Neil Robertson, Cecilia Lindgren, Nigel W. Rayner, Mark I. McCarthy, Erik Ingelsson, Inga Prokopenko
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Reedik Mägi, Krista Fischer, Mart Kals, Tõnu Esko, Markus Perola, Andres Metspalu
Estonian Genome Center, University of Tartu, Tartu, Estonia
Momoko Horikoshi, Neil Robertson, Nigel W. Rayner, Mark I. McCarthy, Inga Prokopenko
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
Antti-Pekka Sarin, Huei-yi Shen, Johannes Kettunen, Jaakko Kaprio, Leif Groop, Samuli Ripatti
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
Gudmar Thorleifsson, Solveig Gretarsdottir, Hilma Holm, Valgerdur Steinthorsdottir, Unnur Thorsteinsdottir, Kari Stefansson
deCODE Genetics, Reykjavik, Iceland
Claes Ladenvall, Valeriya Lyssenko, Marju Orho-Melander, Leif Groop
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University and Skåne University Hospital, Malmö, Sweden
Maris Kuningas, Abbas Dehghan, Renée F. A. G. de Bruijn, M. Arfan Ikram, Oscar H. Franco, Jacqueline Witteman, Albert Hofman
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Harmen H. M. Draisma, Jouke Jan Hottenga, Gonneke Willemsen, Dorret I. Boomsma, Eco J. C. de Geus
Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands
Harmen H. M. Draisma, Jouke Jan Hottenga, Jan H. Smit, Gonneke Willemsen, Brenda W. J. H. Penninx, Dorret I. Boomsma, Eco J. C. de Geus
The EMGO Institute for Health and Care Research, Amsterdam, The Netherlands
Janina S. Ried, Christian Gieger
Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
Natalie R. van Zuydam, Louise A. Donnelly, Alexander S. F. Doney, Colin Neil Alexander Palmer, Andrew D. Morris
Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
Ville Huikari, Marika Kaakinen, Anja Taanila, Marjo-Riitta Järvelin
Institute of Health Sciences, University of Oulu, Oulu, Finland
Massimo Mangino, Kerrin S. Small, Christopher J. Hammond, Tim D. Spector
Department of Twin Research and Genetic Epidemiology, King's College London, United Kingdom
Emily Sonestedt
Diabetes and Cardiovascular Diseases Genetic Epidemiology Research Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden
Beben Benyamin, Nicholas G. Martin, Grant W. Montgomery, John B. Whitfield
Queensland Institute of Medical Research, Herston, Australia
Beben Benyamin
Queensland Brain Institute, University of Queensland, St Lucia, Australia
Christopher P. Nelson, Peter S. Braund, Nilesh J. Samani
Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
Christopher P. Nelson, Nilesh J. Samani
National Institute for Health Research, Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom
Natalia V. Rivera
IRCSS Multimedica, Milan, Italy
Natalia V. Rivera
Institute of Genetics and Biomedical Research, Consiglio Nazionale delle Ricerche, Milan, Italy
Natalia V. Rivera, Najaf Amin, Aaron Isaacs, Lennart C. Karssen, Sara M. Willems, Cornelia M. van Duijn
Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Kati Kristiansson, Aki S. Havulinna, Marja-Liisa Nuotio, Johannes Kettunen, Kari Kuulasmaa, Tiina Laatikainen, Satu Männistö, Markus Perola, Jarmo Virtamo, Veikko Salomaa, Samuli Ripatti
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
Huei-yi Shen
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Abbas Dehghan, Oscar H. Franco, Fernando Rivadeneira, Jacqueline Witteman, Albert Hofman
Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands
Marika Kaakinen, Karl-Heinz Herzig, Markku J. Savolainen, Marjo-Riitta Järvelin
Biocenter Oulu, University of Oulu, Oulu, Finland
Renée F. A. G. de Bruijn, M. Arfan Ikram
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
M. Arfan Ikram
Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands
Anthony J. Balmforth, Alistair S. Hall
Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, School of Medicine, University of Leeds, Leeds, United Kingdom
Angela Döring, H.-Erich Wichmann
Institute of Epidemiology I, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
Angela Döring, Annette Peters
Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
Paul Elliott
MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
Anna-Liisa Hartikainen, Anneli Pouta
Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, University of Oulu, Oulu, Finland
Kauko Heikkilä, Jaakko Kaprio
Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
Karl-Heinz Herzig
Institute of Biomedicine, University of Oulu, Oulu, Finland
Karl-Heinz Herzig
Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
Elina Hyppönen, Chris Power
Centre for Paediatric Epidemiology and Biostatistics and Medical Research Council Centre for the Epidemiology of Child Health, University College London Institute of Child Health, London, United Kingdom
Thomas Illig
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
Thomas Illig
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany
Bo Isomaa
Department of Social Services and Health Care, Jakobstad, Finland
Bo Isomaa, TiinaMaija Tuomi
Folkhälsan Research Centre, Helsinki, Finland
Wolfgang Koenig
Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Ulm, Germany
Jaana Laitinen
Finnish Institute of Occupational Health, Helsinki, Finland
Valeriya Lyssenko
Steno Diabetes Center, Gentofte, Denmark
Esa Läärä
Department of Mathematical Sciences, University of Oulu, Oulu, Finland
Nigel W. Rayner, Samuli Ripatti
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Anneli Pouta, Marjo-Riitta Järvelin
Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland
Wolfgang Rathmann
Institute of Biometrics and Epidemiology, German Diabetes Center, Düsseldorf University, Düsseldorf, Germany
Fernando Rivadeneira, Eric J. G. Sijbrands, Andre G. Uitterlinden
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Aimo Ruokonen
Institute of Diagnostics, University of Oulu, Oulu, Finland
Markku J. Savolainen
Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
Jan H. Smit, Dorret I. Boomsma, Eco J. C. de Geus
Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
Jan H. Smit, Brenda W. J. H. Penninx
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands
Ann-Christine Syvänen
Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Martin D. Tobin
Department of Health Sciences, University of Leicester, Leicester, United Kingdom
Alun Evans
Centre for Public Health, Queen's University of Belfast, Belfast, Northern Ireland
Jean Ferrières
Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
Frank Kee
Centre of Excellence for Public Health Northern Ireland, Queen's University of Belfast, Belfast, Northern Ireland
David-Alexandre Tregouet
Institute of Cardiometabolism and Nutrition, INSERM UMR S937, Pierre and Marie Curie University, Paris, France
Dominique Arveiler
Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France
Philippe Amouyel
Institut Pasteur de Lille, INSERM U744, Université Lille Nord de France, Lille, France
Marco M. Ferrario
Epidemiology and Preventive Medicine Research Centre, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
Paolo Brambilla
Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy
Andrew C. Heath, Pamela A. F. Madden
Washington University School of Medicine, St Louis, Missouri, United States of America
Antti Jula
Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland
Paul Knekt
Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki, Finland
Ben Oostra
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
Cornelia M. van Duijn
Netherlands Genomic Initiative, Leiden, The Netherlands
Cornelia M. van Duijn
Centre for Medical Systems Biology, Leiden, The Netherlands
George Davey Smith
MRC Centre for Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
Jaakko Kaprio
Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
Annette Peters
Munich Heart Alliance, Munich, Germany
H.-Erich Wichmann
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
H.-Erich Wichmann
Klinikum Grosshadern, Munich, Germany
TiinaMaija Tuomi
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
Lars Lind
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Marjo-Riitta Järvelin
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
Erkki Vartiainen
Division of Welfare and Health Promotion, National Institute for Health and Welfare, Helsinki, Finland
Unnur Thorsteinsdottir, Kari Stefansson
Faculty of Medicine, University of Iceland, Reykjavík, Iceland
Mark I. McCarthy
Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
Inga Prokopenko
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom

Corresponding Authors

Competing Interests

TF has received honoraria by MSD for lecturing. GT, SG, VSt, UT, and KS are employees of deCODE Genetics/Amgen, a biotechnology company. OHF is the recipient of a grant from Pfizer Nutrition to establish a new center of ageing research: ErasmusAGE. KH received funding via the Finnish Academy (grant number 129418). JK holds grants from the EU FP7 (funding the present research and other projects), US NIH, the Academy of Finland, and several Finnish Foundations. JK consulted for Pfizer Inc. in 2012 on nicotine dependence. LG, GDS, and MIM are members of the Editorial Board of PLOS Medicine. All other authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: NLP MIM EI IP. Analyzed the data: Meta-analyses: TF SH RM APl KF. Cohort-specific analyses: MH (DIL, WTCCCContr) APS (FTC, FINTWIN, FR, H2000) GT (deCODE) CLa (DGI, MPP, PPP) MKal (EGCUT) MKu (RS) HHMD (NTR) JSR (KORA) NRvZ (GODARTS) VH (NFBC) MM (TwinsUK) ES (MDC-CV) BB (QIMR-AUSTWIN) CPN (GRAPHIC, WTCCCCase) NVR (ERF) KKr (MORGAM) TF (PIVUS, GOSH, TWINGENE, ULSAM) ASHav (FR, H2000) ADe (RS) LAD (GODARTS) MKaa (NFBC) MLN (MORGAM) NR (DIL) RDEB (RS, ERF) AMI (RS, ERF). Statistical insights: APl KF. Contributed reagents/materials/analysis tools: Administrative, technical, or material support: PA DA AJB DIB PB PSB GDS EJCD ASFD ADö PE TE AE MMF JF KF OHF CG SG LG ASHal CJH ALH ACH KH AH KHH HH JJH EH TI EI BI AJ MRJ MKal JKe FK JKe PK WK KKu TL JL LL CLi VL EL PAFM NGM MIM AM GWM ADM SM BO MOM CNAP NLP BWJHP MP APe APo CP IP WR NWR SR FR AR VSa NJS MS HS EJGS KSS JHS TDS KS VSt ACS AT UT MDT DAT TMT AGU CMvD EV JBW HW SMW GW JV JW. Wrote the first draft of the manuscript: TF SH RM APl KF NLP MIM EI IP. Contributed to the writing of the manuscript: TF SH RM APl KF MH APS GT CLa MKal MKu HHMD JSR NRvZ VH MM ES BB CPN NVR KKr HS ASHav ADe LAD MKaa MLN NR RDEB AMI NA AJB PSB ASFD ADö PE TE OHF SG ALH KH KHH HH JJH EH TI AI BI LK JKe WK KKu TL JL CLi VL EL NWR SM APo WR FR AR MS EJGS KSS JHS VSt ACS AT MDT AGU SMW GW JW MP AE JF JV FK DAT DA PA MMF PB ASHal ACH PAFM NGM GWM JBW AJ PK BO CMvD BWJHP GDS JKe NJS CG APe HW DIB EJCD TMT CP CJH TDS LL MOM CNAP ADM LG MRJ VSa EV AH SR AM UT KS NLP MIM EI IP. ICMJE criteria for authorship read and met: TF SH RM APl KF MH APS GT CLa MKal MKu HHMD JSR NRvZ VH MM ES BB CPN NVR KKr HS ASHav ADe LAD MKaa MLN NR RDEB AMI NA AJB PSB ASFD ADö PE TE OHF SG ALH KH KHH HH JJH EH TI AI BI LK JKe WK KKu TL JL CLi VL EL NWR SM APo WR FR AR MS EJGS KSS JHS VSt ACS AT MDT AGU SMW GW JW MP AE JF JV FK DAT DA PA MMF PB ASHal ACH PAFM NGM GWM JBW AJ PK BO CMvD BWJHP GDS JKe NJS CG APe HW DIB EJCD TMT CP CJH TDS LL MOM CNAP ADM LG MRJ VSa EV AH SR AM UT KS NLP MIM EI IP. Agree with manuscript results and conclusions: TF SH RM APl KF MH APS GT CLa MKal MKu HHMD JSR NRvZ VH MM ES BB CPN NVR KKr HS ASHav ADe LAD MKaa MLN NR RDEB AMI NA AJB PSB ASFD ADö PE TE OHF SG ALH KH KHH HH JJH EH TI AI BI LK JKe WK KKu TL JL CLi VL EL NWR SM APo WR FR AR MS EJGS KSS JHS VSt ACS AT MDT AGU SMW GW JW MP AE JF JV FK DAT DA PA MMF PB ASHal ACH PAFM NGM GWM JBW AJ PK BO CMvD BWJHP GDS JKe NJS CG APe HW DIB EJCD TMT CP CJH TDS LL MOM CNAP ADM LG MRJ VSa EV AH SR AM UT KS NLP MIM EI IP. Enrolled patients: Acquisition of data: PA DA AJB DIB PB PSB GDS EJCD ASFD ADö PE TE AE MMF JF KF OHF CG SG LG ASHal CJH ALH ACH KH AH KHH HH JJH EH TI EI BI AJ MRJ MKal JKe FK JKe PK WK KKu TL JL LL CLi VL EL PAFM NGM MIM AM GWM ADM SM BO MOM CNAP NLP BWJHP MP APe APo CP IP WR NWR SR FR AR VSa NJS MS EJGS KSS JHS TDS KS VSt ACS AT UT MDT DAT TMT AGU CMvD EV JBW HW SMW GW JV JW. Obtained funding: PA DA AJB DIB PB PSB GDS EJCD ASFD ADö PE TE AE MMF JF KF OHF CG SG LG ASHal CJH ALH ACH KH AH KHH HH JJH EH TI EI BI AJ MRJ MKal JKe FK JKe PK WK KKu TL JL LL CLi VL EL PAFM NGM MIM AM GWM ADM SM BO MOM CNAP NLP BWJHP MP APe APo CP IP WR NWR SR FR AR VSa NJS MS EJGS KSS JHS TDS KS VSt ACS AT UT MDT DAT TMT AGU CMvD EV JBW HW SMW GW JV JW. Statistical analysis: TF SH RM APl KF NLP MIM EI IP MH APS GT CLa MKal MKu HHMD JSR NRvZ VH MM ES BB CPN NVR KKr ASHav ADe LAD MKaa MLN. Access to all of the data in the study and responsibility for the integrity of the data and the accuracy of the data analysis: TF SH RM APl KF NLP MIM EI IP.