Valérie Turcot, Yingchang Lu, Heather M. Highland, Claudia Schurmann, Anne E. Justice, Rebecca S. Fine, Jonathan P. Bradfield, Tõnu Esko, Ayush Giri, Mariaelisa Graff, Xiuqing Guo, Audrey E. Hendricks, Tugce Karaderi, Adelheid Lempradl, Adam E. Locke, Anubha Mahajan, Eirini Marouli, Suthesh Sivapalaratnam, Kristin L. Young, Tamuno Alfred, Mary F. Feitosa, Nicholas G. D. Masca, Alisa K. Manning, Carolina Medina-Gomez, Poorva Mudgal, Maggie C. Y. Ng, Alex P. Reiner, Sailaja Vedantam, Sara M. Willems, Thomas W. Winkler, Gonçalo Abecasis, Katja K. Aben, Dewan S. Alam, Sameer E. Alharthi, Matthew Allison, Philippe Amouyel, Folkert W. Asselbergs, Paul L. Auer, Beverley Balkau, Lia E. Bang, Inês Barroso, Lisa Bastarache, Marianne Benn, Sven Bergmann, Lawrence F. Bielak, Matthias Blüher, Michael Boehnke, Heiner Boeing, Eric Boerwinkle, Carsten A. Böger, Jette Bork-Jensen, Michiel L. Bots, Erwin P. Bottinger, Donald W. Bowden, Ivan Brandslund, Gerome Breen, Murray H. Brilliant, Linda Broer, Marco Brumat, Amber A. Burt, Adam S. Butterworth, Peter T. Campbell, Stefania Cappellani, David J. Carey, Eulalia Catamo, Mark J. Caulfield, John C. Chambers, Daniel I. Chasman, Yii-Der I. Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y. Chu, Massimiliano Cocca, James P. Cook, Janie Corley, Jordi Corominas Galbany, Amanda J. Cox, David S. Crosslin, Gabriel Cuellar-Partida, Angela D'Eustacchio, John Danesh, Gail Davies, Paul I. W. Bakker, Mark C. H. Groot, Renée Mutsert, Ian J. Deary, George Dedoussis, Ellen W. Demerath, Martin Heijer, Anneke I. Hollander, Hester M. Ruijter, Joe G. Dennis, Josh C. Denny, Emanuele Angelantonio, Fotios Drenos, Mengmeng Du, Marie-Pierre Dubé, Alison M. Dunning, Douglas F. Easton, Todd L. Edwards, David Ellinghaus, Patrick T. Ellinor, Paul Elliott, Evangelos Evangelou, Aliki-Eleni Farmaki, I. Sadaf Farooqi, Jessica D. Faul, Sascha Fauser, Shuang Feng, Ele Ferrannini, Jean Ferrieres, Jose C. Florez, Ian Ford, Myriam Fornage, Oscar H. Franco, Andre Franke, Paul W. Franks, Nele Friedrich, Ruth Frikke-Schmidt, Tessel E. Galesloot, Wei Gan, Ilaria Gandin, Paolo Gasparini, Jane Gibson, Vilmantas Giedraitis, Anette P. Gjesing, Penny Gordon-Larsen, Mathias Gorski, Hans-Jörgen Grabe, Struan F. A. Grant, Niels Grarup, Helen L. Griffiths, Megan L. Grove, Vilmundur Gudnason, Stefan Gustafsson, Jeff Haessler, Hakon Hakonarson, Anke R. Hammerschlag, Torben Hansen, Kathleen Mullan Harris, Tamara B. Harris, Andrew T. Hattersley, Christian T. Have, Caroline Hayward, Liang He, Nancy L. Heard-Costa, Andrew C. Heath, Iris M. Heid, Øyvind Helgeland, Jussi Hernesniemi, Alex W. Hewitt, Oddgeir L. Holmen, G. Kees Hovingh, Joanna M. M. Howson, Yao Hu, Paul L. Huang, Jennifer E. Huffman, M. Arfan Ikram, Erik Ingelsson, Anne U. Jackson, Jan-Håkan Jansson, Gail P. Jarvik, Gorm B. Jensen, Yucheng Jia, Stefan Johansson, Marit E. Jørgensen, Torben Jørgensen, J. Wouter Jukema, Bratati Kahali, René S. Kahn, Mika Kähönen, Pia R. Kamstrup, Stavroula Kanoni, Jaakko Kaprio, Maria Karaleftheri, Sharon L. R. Kardia, Fredrik Karpe, Sekar Kathiresan, Frank Kee, Lambertus A. Kiemeney, Eric Kim, Hidetoshi Kitajima, Pirjo Komulainen, Jaspal S. Kooner, Charles Kooperberg, Tellervo Korhonen, Peter Kovacs, Helena Kuivaniemi, Zoltán Kutalik, Kari Kuulasmaa, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, David Lamparter, Ethan M. Lange, Leslie A. Lange, Claudia Langenberg, Eric B. Larson, Nanette R. Lee, Terho Lehtimäki, Cora E. Lewis, Huaixing Li, Jin Li, Ruifang Li-Gao, Honghuang Lin, Keng-Hung Lin, Li-An Lin, Xu Lin, Lars Lind, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Dajiang J. Liu, Yongmei Liu, Ken S. Lo, Artitaya Lophatananon, Andrew J. Lotery, Anu Loukola, Jian'An Luan, Steven A. Lubitz, Leo-Pekka Lyytikäinen, Satu Männistö, Gaëlle Marenne, Angela L. Mazul, Mark I. McCarthy, Roberta McKean-Cowdin, Sarah E. Medland, Karina Meidtner, Lili Milani, Vanisha Mistry, Paul Mitchell, Karen L. Mohlke, Leena Moilanen, Marie Moitry, Grant W. Montgomery, Dennis O. Mook-Kanamori, Carmel Moore, Trevor A. Mori, Andrew D. Morris, Andrew P. Morris, Martina Müller-Nurasyid, Patricia B. Munroe, Mike A. Nalls, Narisu Narisu, Christopher P. Nelson, Matt Neville, Sune F. Nielsen, Kjell Nikus, Pål R. Njølstad, Børge G. Nordestgaard, Dale R. Nyholt, Jeffrey R. O'Connel, Michelle L. O'Donoghue, Loes M. Olde Loohuis, Roel A. Ophoff, Katharine R. Owen, Chris J. Packard, Sandosh Padmanabhan, Colin N. A. Palmer, Nicholette D. Palmer, Gerard Pasterkamp, Aniruddh P. Patel, Alison Pattie, Oluf Pedersen, Peggy L. Peissig, Gina M. Peloso, Craig E. Pennell, Markus Perola, James A. Perry, John R. B. Perry, Tune H. Pers, Thomas N. Person, Annette Peters, Eva R. B. Petersen, Patricia A. Peyser, Ailith Pirie, Ozren Polasek, Tinca J. Polderman, Hannu Puolijoki, Olli T. Raitakari, Asif Rasheed, Rainer Rauramaa, Dermot F. Reilly, Frida Renström, Myriam Rheinberger, Paul M. Ridker, John D. Rioux, Manuel A. Rivas, David J. Roberts, Neil R. Robertson, Antonietta Robino, Olov Rolandsson, Igor Rudan, Katherine S. Ruth, Danish Saleheen, Veikko Salomaa, Nilesh J. Samani, Yadav Sapkota, Naveed Sattar, Robert E. Schoen, Pamela J. Schreiner, Matthias B. Schulze, Robert A. Scott, Marcelo P. Segura-Lepe, Svati H. Shah, Wayne H.-H. Sheu, Xueling Sim, Andrew J. Slater, Kerrin S. Small, Albert V. Smith, Lorraine Southam, Timothy D. Spector, Elizabeth K. Speliotes, John M. Starr, Kari Stefansson, Valgerdur Steinthorsdottir, Kathleen E. Stirrups, Konstantin Strauch, Heather M. Stringham, Michael Stumvoll, Liang Sun, Praveen Surendran, Amy J. Swift, Hayato Tada, Katherine E. Tansey, Jean-Claude Tardif, Kent D. Taylor, Alexander Teumer, Deborah J. Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Betina H. Thuesen, Anke Tönjes, Gerard Tromp, Stella Trompet, Emmanouil Tsafantakis, Jaakko Tuomilehto, Anne Tybjaerg-Hansen, Jonathan P. Tyrer, Rudolf Uher, André G. Uitterlinden, Matti Uusitupa, Sander W. Laan, Cornelia M. Duijn, Nienke Leeuwen, Jessica Van Setten, Mauno Vanhala, Anette Varbo, Tibor V. Varga, Rohit Varma, Digna R. Velez Edwards, Sita H. Vermeulen, Giovanni Veronesi, Henrik Vestergaard, Veronique Vitart, Thomas F. Vogt, Uwe Völker, Dragana Vuckovic, Lynne E. Wagenknecht, Mark Walker, Lars Wallentin, Feijie Wang, Carol A. Wang, Shuai Wang, Yiqin Wang, Erin B. Ware, Nicholas J. Wareham, Helen R. Warren, Dawn M. Waterworth, Jennifer Wessel, Harvey D. White, Cristen J. Willer, James G. Wilson, Daniel R. Witte, Andrew R. Wood, Ying Wu, Hanieh Yaghootkar, Jie Yao, Pang Yao, Laura M. Yerges-Armstrong, Robin Young, Eleftheria Zeggini, Xiaowei Zhan, Weihua Zhang, Jing Hua Zhao, Wei Zhao, Wei Zhou, Krina T Zondervan, Jerome I. Rotter, John A. Pospisilik, Fernando Rivadeneira, Ingrid B. Borecki, Panos Deloukas, Timothy M. Frayling, Guillaume Lettre, Kari E. North, Cecilia M. Lindgren, Joel N. Hirschhorn, Ruth J. F. Loos
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity. © 2017 The Author(s).
Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, United States; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, United States; Human Genetics Center, University of Texas School of Public Health, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States; Broad Institute of MIT and Harvard, Cambridge, MA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, United States; Center for Applied Genomics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Quantinuum Research, LLC, San Diego, CA, United States; Estonian Genome Center, University of Tartu, Tartu, Estonia; Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, United States; Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States; Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Department of Mathematical and Statistical Sciences, University of Colorado, Denver, CO, United States; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University, Famagusta, Cyprus; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, United States; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Vascular Medicine, AMC, Amsterdam, Netherlands; Massachusetts General Hospital, Boston, MA, United States; Department of Haematology, University of Cambridge, Cambridge, United Kingdom; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom; Department of Medicine, Harvard Medical School, Boston, MA, United States; Medical and Population Genetics Program, Broad Institute, Cambridge, MA, United States; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, United Kingdom; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany; Netherlands Comprehensive Cancer Organisation, Utrecht, Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands; School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, ON, Canada; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia; Department of Family Medicine and Public Health, University of California, San Diego, San Diego, CA, United States; INSERM U1167, Lille, France; Institut Pasteur de Lille, Lille, U1167, France; Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, United States; INSERM U1018, Centre de Recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, United States; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States; IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany; Department of Medicine, University of Leipzig, Leipzig, Germany; Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany; School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, United States; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; NIHR Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, United Kingdom; Marshfield Clinic Research Institute, Marshfield, WI, United States; Department of Medical Sciences, University of Trieste, Trieste, Italy; Department of Medicine, University of Washington, Seattle, WA, United States; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Epidemiology Research Program, American Cancer Society, Atlanta, GA, United States; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; Weis Center for Research, Geisinger Health System, Danville, PA, United States; NIHR Barts Cardiovascular Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex, United Kingdom; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Harvard Medical School, Boston, MA, United States; Medical Department, Lillebaelt Hospital, Vejle, Denmark; NHLBI Framingham Heart Study, Framingham, MA, United States; Genetics and Pharmacogenomics, Merck, Sharp and Dohme, Boston, MA, United States; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD, United States; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands; Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands; Menzies Health Institute Queensland, Griffith University, Southport, QLD, Australia; Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, United States; Diamantina Institute, University of Queensland, Brisbane, QLD, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands; Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands; Utrecht Institute for Pharmaceutical Sciences, Division Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States; Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands; Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom; Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Health Sciences, University of Leicester, Leicester, United Kingdom; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United States; Department of Ophthalmology, University of Cologne, Cologne, Germany; CNR Institute of Clinical Physiology, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Toulouse University School of Medicine, Toulouse, France; University of Glasgow, Glasgow, United Kingdom; Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, United States; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, United States; Department of Public Health and Clinical Medicine, Unit of Medicine, Umeå University, Umeå, Sweden; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Research Unit, AREA Science Park, Trieste, Italy; Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom; Geriatrics, Department of Public Health, Uppsala University, Uppsala, Sweden; Carolina Population Center, University of North Carolina, Chapel Hill, NC, United States; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Vision Sciences, Clinical Neurosciences Research Group, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, Netherlands; Department of Sociology, University of North Carolina, Chapel Hill, NC, United States; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Bethesda, MD, United States; University of Exeter Medical School, University of Exeter, Exeter, United Kingdom; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC, United States; Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Neurology, Boston University School of Medicine, Boston, MA, United States; Department of Psychiatry, Washington University, St. Louis, MO, United States; Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Cardiology, Heart Center, Tampere University Hospital, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, VIC, Australia; Centre for Ophthalmology and Vision Science, Lions Eye Institute, University of Western Australia, Perth, WA, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, Australia; KG Jebsen Center for Genetic Epidemiology, Department of Public Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China; Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States; Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; Research Unit Skellefteå, Skellefteå, Sweden; Department of Genome Sciences, University of Washington, Seattle, WA, United States; Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark; Faculty of Medicine, Aalborg University, Aalborg, Denmark; Research Center for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States; Centre for Brain Research, Indian Institute of Science, Bangalore, India; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands; Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Echinos Medical Centre, Echinos, Greece; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, United Kingdom; UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast, United Kingdom; Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States; Department of Health Services, University of Washington, Seattle, WA, United States; Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines; USC-Office of Population Studies Foundation,Inc., University of San Carlos, Cebu City, Philippines; Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, United States; Department of Medicine, Boston University School of Medicine, Boston, MA, United States; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States; Department of Public Health Sciences, Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, PA, United States; Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States; Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, United Kingdom; Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany; German Center for Diabetes Research, Neuherberg, Germany; Westmead Millennium Institute of Medical Research, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, NSW, Australia; Department of Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France; Department of Public Health, University Hospital of Strasbourg, Strasbourg, France; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands; INTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Department of Medicine i, University Hospital Großhadern, Ludwig-Maximilians-Universitat, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, MD, United States; Data Tecnica International, Glen Echo, MD, United States; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; Program for Personalized and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, United States; Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee, United Kingdom; Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands; School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia; Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark; School of Medicine, University of Split, Split, Croatia; Central Hospital of Southern Ostrobothnia, Seinäjoki, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Centre for Non-Communicable Diseases Pakistan, Karachi, Pakistan; Department of Biobank Research, Umeå University, Umeå, Sweden; Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; NHS Blood and Transplant-Oxford Centre, Oxford, United Kingdom; BRC Haematology Theme and Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Public Health and Clinical Medicine, Unit of Family Medicine, Umeå University, Umeå, Sweden; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom; Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Departments of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States; Duke Molecular Physiology Institute, Duke University, Durham, NC, United States; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore; Genetics, Target Sciences, GlaxoSmithKline, Research Triangle Park, NC, United States; OmicSoft at Qiagen Company, Cary, NC, United States; Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom; DeCODE Genetics/Amgen, Inc., Reykjavik, Iceland; Department of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Munich, Germany; Kanazawa University, Kanazawa, Japan; College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Center for Pediatric Research, Department for Women's and Child Health, University of Leipzig, Leipzig, Germany; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands; Anogia Medical Centre, Anogia, Greece; Centre for Vascular Prevention, Danube University Krems, Krems, Austria; Dasman Diabetes Institute, Dasman, Kuwait; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada; Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, Netherlands; Primary Health Care Unit, Central Hospital of Central Finland, Jyväskylä, Finland; Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland; USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States; Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, United States; Research Center on Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Cardiometabolic Disease, Merck, Sharp and Dohme, Kenilworth, NJ, United States; German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle, United Kingdom; Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Genetics, Target Sciences, GlaxoSmithKline, King of Prussia, PA, United States; Departments of Epidemiology and Medicine, Diabetes Translational Research Center, Fairbanks School of Public Health and School of Medicine, Indiana University, Indianapolis, IN, United States; Green Lane Cardiovascular Service, Auckland City Hospital, University of Auckland, Auckland, New Zealand; Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States; Danish Diabetes Academy, Odense, Denmark; Department of Public Health, Aarhus University, Aarhus, Denmark; GlaxoSmithKline, King of Prussia, PA, United States; Department of Clinical Sciences, Quantitative Biomedical Research Center, Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, United States; Endometriosis CaRe Centre, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom; Department of Epidemiology, Carolina Center of Genome Sciences, Chapel Hill, NC, United States; Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, United Kingdom; Department of Pediatrics, Harvard Medical School, Boston, MA, United States; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
