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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

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  • 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

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  • 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

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  • Alexander Ploner,

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

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  • Krista Fischer,

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

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  • 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

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  • Antti-Pekka Sarin,

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

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  • Gudmar Thorleifsson,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • Claes Ladenvall,

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

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  • Mart Kals,

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

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  • Maris Kuningas,

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

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  • 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

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  • Janina S. Ried,

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

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  • Natalie R. van Zuydam,

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

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  • Ville Huikari,

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

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  • Massimo Mangino,

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

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  • Emily Sonestedt,

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

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  • Beben Benyamin,

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

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  • 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

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  • 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

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  • Kati Kristiansson,

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

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  • 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

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  • Aki S. Havulinna,

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

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  • Abbas Dehghan,

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

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  • Louise A. Donnelly,

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

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  • Marika Kaakinen,

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

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  • Marja-Liisa Nuotio,

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

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  • 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

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  • 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

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  • 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

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  • Najaf Amin,

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

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  • Anthony J. Balmforth,

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

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  • Peter S. Braund,

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

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  • Alexander S. F. Doney,

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

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  • 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

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  • 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

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  • Tõnu Esko,

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

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  • Oscar H. Franco,

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

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  • Solveig Gretarsdottir,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • Anna-Liisa Hartikainen,

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

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  • Kauko Heikkilä,

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

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  • 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

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  • Hilma Holm,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • 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

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  • 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

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  • 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

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  • Aaron Isaacs,

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

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  • Bo Isomaa,

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

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  • Lennart C. Karssen,

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

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  • 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

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  • Wolfgang Koenig,

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

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  • Kari Kuulasmaa,

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

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  • Tiina Laatikainen,

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

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  • Jaana Laitinen,

    Affiliation: Finnish Institute of Occupational Health, Helsinki, Finland

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  • Cecilia Lindgren,

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

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  • 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

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  • Esa Läärä,

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

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  • 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

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  • Satu Männistö,

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

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  • 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

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  • Wolfgang Rathmann,

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

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  • Fernando Rivadeneira,

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

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  • Aimo Ruokonen,

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

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  • Markku J. Savolainen,

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

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  • Eric J. G. Sijbrands,

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

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  • Kerrin S. Small,

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

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  • 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

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  • Valgerdur Steinthorsdottir,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • Ann-Christine Syvänen,

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

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  • Anja Taanila,

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

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  • Martin D. Tobin,

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

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  • Andre G. Uitterlinden,

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

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  • Sara M. Willems,

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

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  • Gonneke Willemsen,

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

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  • Jacqueline Witteman,

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

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  • Markus Perola,

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

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  • Alun Evans,

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

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  • Jean Ferrières,

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

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  • Jarmo Virtamo,

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

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  • Frank Kee,

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

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  • David-Alexandre Tregouet,

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

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  • Dominique Arveiler,

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

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  • Philippe Amouyel,

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

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  • Marco M. Ferrario,

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

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  • Paolo Brambilla,

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

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  • Alistair S. Hall,

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

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  • Andrew C. Heath,

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

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  • Pamela A. F. Madden,

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

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  • Nicholas G. Martin,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

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  • Grant W. Montgomery,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

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  • John B. Whitfield,

    Affiliation: Queensland Institute of Medical Research, Herston, Australia

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  • Antti Jula,

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

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  • Paul Knekt,

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

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  • Ben Oostra,

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

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  • 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

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  • 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

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  • George Davey Smith,

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

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  • 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

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  • 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

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  • Christian Gieger,

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

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  • Annette Peters,

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

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  • 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

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  • 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

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  • 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

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  • TiinaMaija Tuomi,

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

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  • 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

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  • Christopher J. Hammond,

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

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  • Tim D. Spector,

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

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  • Lars Lind,

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

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  • Marju Orho-Melander,

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

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  • Colin Neil Alexander Palmer,

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

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  • Andrew D. Morris,

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

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  • 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

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  • 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

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  • Veikko Salomaa,

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

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  • Erkki Vartiainen,

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

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  • Albert Hofman,

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

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  • 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

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  • Andres Metspalu,

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

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  • Unnur Thorsteinsdottir,

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

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  • Kari Stefansson,

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

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  • Nancy L. Pedersen ,

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

    These authors are joint senior authors on this work.

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  • 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.

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  • 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.

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  • 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

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