Shweta Ramdas, Jonathan Judd, Sarah E. Graham, Stavroula Kanoni, Yuxuan Wang, Ida Surakka, Brandon Wenz, Shoa L. Clarke, Alessandra Chesi, Andrew Wells, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W. Winkler, Adam E. Locke, Eirini Marouli, Greg J.M. Zajac, Kuan-Han H. Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T. Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F. Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M. Brumpton, Humaira Rasheed, Aki S. Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A. Rosenthal, Todd Lingren, QiPing Feng, Iftikhar J. Kullo, Akira Narita, Jun Takayama, Hilary C. Martin, Karen A. Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E. Miller, Archie Campbell, Kuang Lin, Iona Y. Millwood, Asif Rasheed, George Hindy, Jessica D. Faul, Wei Zhao, David R. Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R. Brown, Weihua Zhang, Ketian Yu, Ellen M. Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian'an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R. Wood, Yingji Ji, Zishan Gao, Simon Haworth, Ruth E. Mitchell, Jin Fang Chai, Mette Aadahl, Anne A. Bjerregaard, Jie Yao, Ani Manichaikul, Wen-Jane Lee, Chao Agnes Hsiung, Helen R. Warren, Julia Ramirez, Jette Bork-Jensen, Line L. Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F. McDaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T. Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Sebastian Schönherr, Lukas Forer, Markus Scholz, Tessel E. Galesloot, Jonathan P. Bradfield, Sanni E. Ruotsalainen, E. Warwick Daw, Joseph M. Zmuda, Jonathan S. Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A. Brody, Phuong Le, Mary F. Feitosa, Mary K. Wojczynski, Daiane Hemerich, Michael Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W. Benjamins, Jorgen Engmann, Tsao L. Noah, Anurag Verma, Roderick C. Slieker, Ken Sin Lo, Nuno R. Zilhao, Marcus E. Kleber, Graciela E. Delgado, Shaofeng Huo, Daisuke D. Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L. Leonard, Jonathan Marten, Carina Emmel, Börge Schmidt, Laura J. Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S. Nongmaithem, Alagu Sankareswaran, Marguerite R. Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R.H.J. Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A. Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N. Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C. Warner, Ya Xing Wang, Wen B. Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A. Kentistou, Bernhard Banas, Anna Morgan, Karina Meidtner, Lawrence F. Bielak, Jennifer A. Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J. van der Most, Niina Pitkänen, Brian E. Cade, Sander W. van der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R. Bentley, Ayo P. Doumatey, Adebowale A. Adeyemo, Jong Young Lee, Eva R.B. Petersen, Aneta A. Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W. Rayner, Carol A. Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O. Obura, Jessica van Setten, Karen Y. He, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D. Jackson, Alexander P. Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C. Bis, Lenore J. Launer, Huaixing Li, Mike A. Nalls, Olli T. Raitakari, Sahoko Ichihara, Sarah H. Wild, Christopher P. Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S. Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique de Kleijn, Gert J. de Borst, Eung Kweon Kim, Hieab H.H. Adams, M. Arfan Ikram, Xiaofeng Zhu, Folkert W. Asselbergs, Adriaan O. Kraaijeveld, Joline W.J. Beulens, Xiao-Ou Shu, Loukianos S. Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W. Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E. Pennell, Trevor A. Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M. Heid, Klaus J. Stark, Martina E. Zimmermann, Henry Völzke, Georg Homuth, Michele K. Evans, Alan B. Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E. Hoefer, Susan Redline, Katja Pahkala, Albertine J. Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Patricia A. Peyser, Norihiro Kato, Matthias B. Schulze, Giorgia Girotto, Carsten A. Böger, Bettina Jung, Peter K. Joshi, David A. Bennett, Philip L. De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J. Caulfield, Patricia B. Munroe, Xiuqing Guo, Marina Ciullo, Jost B. Jonas, Nilesh J. Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A. Aguilar-Salinas, Linda S. Adair, Sonny Augustin Bechayda, H. Janaka de Silva, Ananda R. Wickremasinghe, Ronald M. Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke I. den Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G. Wilson, Lars Lind, Chew-Kiat Heng, Amanda E. Nelson, Yvonne M. Golightly, James F. Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J. Scott, D.C. Rao, Donna K. Arnett, Mark Walker, Laura J. Scott, Heikki A. Koistinen, Giriraj R. Chandak, Josep M. Mercader, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, E. Shyong Tai, Rob M. van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F. Reilly, Amy Jayne McKnight, Frank Kee, Karl-Heinz Jöckel, Mark I. McCarthy, Colin N.A. Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M. van Duijn, Zi-Bing Jin, Fan Lu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M. t Hart, Petra J.M. Elders, Daniel J. Rader, Scott M. Damrauer, Meena Kumari, Mika Kivimaki, Pim van der Harst, Tim D. Spector, Ruth J.F. Loos, Michael A. Province, Esteban J. Parra, Miguel Cruz, Bruce M. Psaty, Ivan Brandslund, Peter P. Pramstaller, Charles N. Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F.A. Grant, Lambertus Kiemeney, Jacqueline de Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W. Franks, Allan Linneberg, J. Wouter Jukema, Amit V. Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O. Mook-Kanamori, Ko Willems van Dijk, Hugh Watkins, David P. Strachan, Niels Grarup, Peter Sever, Neil Poulter, Wayne Huey-Herng Sheu, Jerome I. Rotter, Thomas M. Dantoft, Fredrik Karpe, Matt J. Neville, Nicholas J. Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T. Hattersley, Nancy L. Pedersen, Patrik K.E. Magnusson, Dorret I. Boomsma, Eco J.C. de Geus, L. Adrienne Cupples, Joyce B.J. van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J. Wareham, Claudia Langenberg, Eleftheria Zeggini, Jaakko Tuomilehto, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C. Chambers, Jaspal S. Kooner, Paul S. de Vries, Alanna C. Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E. North, Martha Daviglus, Peter Kraft, Nicholas G. Martin, John B. Whitfield, Shahid Abbas, Danish Saleheen, Robin G. Walters, Michael V. Holmes, Corri Black, Blair H. Smith, Aris Baras, Anne E. Justice, Julie E. Buring, Paul M. Ridker, Daniel I. Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A. van Heel, Richard C. Trembath, Wei-Qi Wei, Gail P. Jarvik, Bahram Namjou, M. Geoffrey Hayes, Marylyn D. Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, Y. Eugene Chen, Yuk-Lam Ho, Julie A. Lynch, Philip S. Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J. O'Donnell, John M. Gaziano, Peter Wilson, Karen L. Mohlke, Timothy M. Frayling, Joel N. Hirschhorn, Sekar Kathiresan, Michael Boehnke, Struan Grant, Pradeep Natarajan, Yan V. Sun, Andrew P. Morris, Panos Deloukas, Gina Peloso, Themistocles L. Assimes, Cristen J. Willer, Xiang Zhu, Christopher D. Brown
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology. © 2022 American Society of Human Genetics
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, United States; Department of Genetics, Stanford University School of Medicine, Stanford, 94305, CA, United States; Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, 48109, MI, United States; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, United Kingdom; Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, 02118, MA, United States; VA Palo Alto Health Care Systems, Palo Alto, CA, United States; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, 94305, CA, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States; Endocrinology, Boston Childrens Hospital, Boston, 02115, MA, United States; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, 75 Ames street, Cambridge, 02142, MA, United States; Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany; McDonnell Genome Institute and Department of Medicine, Washington University, St. Louis, 63108, MO, United States; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, United States; Atlanta VA Health Care System, Decatur, GA, United States; Malcolm Randall VA Medical Center, Gainesville, FL, United States; Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States; deCODE genetics/Amgen, Inc., Sturlugata 8, Reykjavik, 102, Iceland; School of Engineering and Natural Sciences, University of Iceland, Sæmundargötu 2, Reykjavik, 102, Iceland; Department of Clinical Biochemistry, Landspitali - National University Hospital of Iceland, Hringbraut, Reykjavik, 101, Iceland; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Chungbuk, South Korea; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, The University of Tokyo, Tokyo, Japan; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom; Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Tukholmankatu 8, Helsinki, 00014, Finland; Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Genetics, Institute for Biomedical Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, 19104, PA, United States; Center for Genetic Medicine, Northwestern University, Feinberg School of Medicine, Chicago, 60611, IL, United States; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, United States; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Cardiovascular Medicine and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, United States; Tohoku Medical Megabank Organization, Tohoku University, Sendai, 980-8573, Japan; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, 98109, WA, United States; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, United States; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom; Usher Institute, The University of Edinburgh, Nine, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, United Kingdom; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, United Kingdom; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, United Kingdom; Center for Non-Communicable Diseases, Karachi, SD, Pakistan & Faisalabad Institute of Cardiology, Faislabad, Pakistan; Department of Population Medicine, Qatar University College of Medicine, QU Health, Doha, Qatar; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48104, MI, United States; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, United States; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, 02115, MA, United States; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, 77030, TX, United States; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, United Kingdom; Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, Middlesex, UB1 3HW, United Kingdom; Imperial College Healthcare NHS Trust, Imperial College London, London, W12 0HS, United Kingdom; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, CB2 0QQ, United Kingdom; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort's Causeway, Cambridge, CB1 8RN, United Kingdom; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, Netherlands; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, United Kingdom; Department of Clinical Acupuncture and Moxibustion, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, 210029, China; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Bristol Dental School, University of Bristol, Lower Maudlin Street, Bristol, BS1 2LY, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield Grove, Bristol, BS8 2BN, United Kingdom; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovations (Formerly LABioMed) at Harbor-UCLA Medical Center, Torrance, 90502, CA, United States; Center for Public Health Genomics, University of Virginia, Charlottesville, 22903, VA, United States; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; No. 1650, Sec. 4, Taiwan Boulevard, Taichung City, 40705, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Miaoli County, Zhunan Town, 350, Taiwan; NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom; Unit of Genomics of Complex Diseases. Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain; Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Rome, Italy; Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sardinia, Italy; University Center for Primary Care and Public Health, University of Lausanne, Rte de Berne 113, Lausanne, 1010, Switzerland; Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, Lausanne, 1011, Switzerland; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, United Kingdom; Institute for Cardiogenetics, University of Lübeck, DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, University Heart Center Lübeck, Lübeck and Charité – University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany; Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., partner site Munich Heart Alliance, Munich, Germany; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Lund University Diabetes Centre, Lunds University, Malmö, Sweden; Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria and German Chronic Kidney Disease Study, Austria; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, Leipzig, 04107, Germany; LIFE Research Centre for Civilization Diseases, University of Leipzig, Philipp-Rosenthal-Straße 27, Leipzig, 04103, Germany; Radboud university medical center, Radboud Institute for Health Sciences, Nijmegen, Netherlands; Quantinuum Research LLC, Wayne, 19087, PA, United States; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, 15232, PA, United States; Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Via Galvani 31, Bolzano, 39100, Italy; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98101, WA, United States; Department of Anthropology, University of Toronto at Mississauga, Mississauga, L5L 1C6, ON, Canada; Department of Computer Science, University of Toronto, Toronto, M5S 2E4, ON, Canada; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, United Kingdom; NIHR Biomedical Research Centre at Guy's and St Thomas’ Foundation Trust, London, SE1 9RT, United Kingdom; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, 9700RB, Netherlands; Institute of Cardiovascular Sciences, University College London, Gower Street, London, WC1E 6BT, United Kingdom; Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, United Kingdom; Department of Surgery, University of Pennsylvania, Philadelphia, 19104, PA, United States; Amsterdam UMC, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam, 1081HV, Netherlands; Leiden University Medical Center, Department of Cell and Chemical Biology, Leiden, 2333ZA, Netherlands; Montreal Heart Institute, Université de Montréal, 5000 Belanger street, Montreal, H1T1C8, QC, Canada; Icelandic Heart Association, 201 Kopavogur, Iceland; Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany; SYNLAB MVZ Humangenetik Mannheim GmbH, Mannheim, 68163, Germany; Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Biomedical Technology Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan; School of Life Sciences, Westlake University, Zhejiang, Hangzhou, 310024, China; Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, QLD, Australia; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Section of Statistical Multi-omics, Department of Clinical and Experimental research, University of Surrey, Guildford, Surrey, United Kingdom; Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, United States; Data Tecnica International, Glen Echo, MD, United States; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom; Institute for Medical Informatics, Biometrie and Epidemiology, University of Duisburg-Essen, Essen, Germany; Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer-University of Granada-Andalusian Regional Government, Granada, Spain; Hematology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, 461-8673, Japan; University of Alabama at Birmingham, Epidemiology, School of Public Health, Birmingham, AL, United States; Tampere Centre for Skills Training and Simulation, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, 77030, TX, United States; CONACYT, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de Mexico, Mexico; Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica, Ciudad de Mexico, Mexico; Center for diabetes research, University of Bergen, Bergen, Norway; Genomic Research on Complex diseases (GRC Group), CSIR-Centre for Cellular and Molecular Biology, Telangana, Hyderabad, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre, New Delhi, India; Hunter Medical Research Institute, Newcastle, NSW, Australia; Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, South Korea; Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, 06355, South Korea; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 04514, South Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, South Korea; Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, United States; Health Services and Systems Research, Duke-NUS Medical School, 169857, Singapore; Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado, Denver, Aurora, 80045, CO, United States; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110020, India; Departments of Ophthalmology and Human Genetics, Radboud University Nijmegen Medical Center, Philips van Leydenlaan 15, Nijmegen, 6525 EX, Netherlands; Vanderbilt Epidemiology Center, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Pediatrics, University of California San Francisco, Oakland, 94609, CA, United States; National Center for Global Health and Medicine, Tokyo, 1628655, Japan; Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States; Department of Biostatistics and Epidemiology, University of Massachusetts-Amherst, Amherst, 01003, MA, United States; Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom; Beijing Institute of Ophthalmology, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, 17 Hougou Lane, Chong Wen Men, Beijing, 100005, China; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, China; Institute of Genetics and Biophysics “Adriano Buzzati-Traverso” - CNR, Naples, Italy; IRCCS Neuromed, Isernia, Pozzilli, Italy; Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, United States; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States; Department of Nephrology, University Hospital Regensburg, Regensburg, Germany; Institute for Maternal and Child Health—IRCCS, Burlo Garofolo, Trieste, 34127, Italy; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Eleftheriou Venizelou, Athens, Greece; Department of Population Science and Experimental Medicine, University College London, London, United Kingdom; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria; Massachusetts General Hospital Cancer Center, Charlestown, 02129, MA, United States; Institute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Sassari, Sassari, Italy; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, Netherlands; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Sleep Medicine and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, United States; Division of Sleep Medicine, Harvard Medical School, Boston, 02115, MA, United States; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical genetics, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Laboratory of Epidemiology and Population Science National Institute on Aging Intramural Research Program, NIH 251 Bayview Blvd, NIH Biomedical Research Center, Baltimore, 21224, MD, United States; Fels Cancer Institute for Personalized Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald and University Medicine Greifswald, Greifswald, Germany; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, 20892, MD, United States; Oneomics. co. ltd. 2F, Soonchunhyang Mirai Medical Center 173, Buheuyng-ro, Bucheon-si Gyeonggi-do, 14585, South Korea; Department of Clinical Biochemistry and Immunology, Hospital of Southern Jutland, Kresten Philipsens Vej 15, Aabenraa, 6200, Denmark; Department of Clinical Biochemistry, Lillebaelt Hospital, Kolding, Denmark; Department of Biomedical Science, Hallym University, Gangwon, Chuncheon, 24252, South Korea; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany; Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany; Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom; School of Medicine and Public Health, Faculty of Medicine and Health, University of Newcastle, Newcastle, 2308, NSW, Australia; Center for Geriatrics and Gerontology, Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Kinesiology, Université Laval, Quebec City, QC, Canada; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33014, Finland; Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, 33521, Finland; Department of Cardiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33014, Finland; University of Queensland Diamantina Institute, Translational Research Institute, Kent St, Woolloongabba, Brisbane, 4102, QLD, Australia; Department of Medicine, Bornholms Hospital, Rønne, Denmark; School of Public Health, University of Alabama at Birmingham, Birmingham, AL, United States; Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106, OH, United States; Ohio State University, Division of Endricinology, Columbus, 43210, OH, United States; University of Washington, Department of Epidemiology, Seattle, 98195, WA, United States; George Washington University, School of Medicine and Health Sciences, Washington, 20037, DC, United States; Department of Epidemiology, School of Public Health, Peking University Health Science Center, Beijing, China; Institute for Laboratory Medicine, University Hospital Leipzig, Paul-List-Strasse 13/15, Leipzig, 04103, Germany; Laboratory of Epidemiology and Population Sciences, National Institute on Aging Intramural Research Program, NIH, Baltimore, 20892-9205, MD, United States; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, 329-0498, Japan; Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Department of Functional Pathology, Shimane University School of Medicine, Izumo, 6938501, Japan; Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland; Department of Physiology, University of Turku, Turku, Finland; Faculty of Medicine, University of Split, Šoltanska 2, Split, 21000, Croatia; Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Liebigstr. 21, Leipzig, 04103, Germany; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, 5650871, Japan; Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, 5650871, Japan; Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, 03722, South Korea; Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Ceslrntre Utrecht, Utrecht, 3584CG, Netherlands; Second Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece; Center for Vision Research, Department of Ophthalmology and The Westmead Institute, University of Sydney, Hawkesbury Rd, Sydney, 2145, NSW, Australia; Menzies Institute for Medical Research, School of Medicine, University of Tasmania, Liverpool St, Hobart, 7000, TAS, Australia; Centre for Eye Research Australia, University of Melbourne, Melbourne, 3002, VIC, Australia; Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33014, Finland; Centre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Quebec, QC, Canada; Pennington Biomedical Research Center, Baton Rouge, 70808, LA, United States; Discipline of Internal Medicine, Medical School, The University of Western Australia, Perth, WA, Australia; Institute of Epidemiology, Kiel University, Kiel, Germany; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany; Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden; Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine, EwhaWomans University School of Medicine, Seoul, South Korea; Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, 15232, PA, United States; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A∗STAR), Singapore, 117609, Singapore; Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, 02447, South Korea; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Algebra University College, Ilica 242, Zagreb, Croatia; Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, Netherlands; Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria; Local Health Unit Toscana Centro, Firenze, Italy; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany; Department of Medicine, Surgery and Health Sciences, University of Trieste, Strada di Fiume 447, Trieste, 34149, Italy; Department of Nephrology, Diabetology, Rheumatology, Traunstein Hospital, Traunstein, Germany; KfH Kidney Center Traunstein, Traunstein, Germany; Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, United States; Medical School, National and Kapodistrian University Athens, 75 M. Assias Street, Athens, 115 27, Greece; Dromokaiteio Psychiatric Hospital, Athens, 124 61, Greece; Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Kutzerufer 1, Mannheim, 68167, Germany; Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland; Privatpraxis Prof Jonas und Dr Panda-Jonas, Heidelberg, Germany; Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States; Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico; Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico; Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 27599, NC, United States; Carolina Population Center, University of North Carolina, Chapel Hill, 27516, NC, United States; USC–Office of Population Studies Foundation, University of San Carlos, Cebu City, 6000, Philippines; Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, 6000, Philippines; Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, 11010, Sri Lanka; Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, 11010, Sri Lanka; Children's Hospital Oakland Research Institute, Oakland, 94609, CA, United States; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India; Department of Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, United States; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, 39216, MS, United States; Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, Singapore; Department of Medicine, University of North Carolina, Chapel Hill, NC, United States; Injury Prevention Research Center, University of North Carolina, Chapel Hill, NC, United States; Division of Physical Therapy, University of North Carolina, Chapel Hill, NC, United States; Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, VU Medical Center Amsterdam, Amsterdam, Netherlands; Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; University of Kentucky, College of Public Health, Lexington, KY, United States; Institute of Cellular Medicine (Diabetes), The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom; University of Helsinki and Department of Medicine, Helsinki University Hospital, P.O.Box 340, Haartmaninkatu 4, Helsinki, 00029, Finland; Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, Helsinki, 00290, Finland; JSS Academy of Higher Education and Research, Mysuru, India; Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, 02115, MA, United States; Dirección de Nutrición and Unidad de Estudios de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Instituto Nacional de Salud Publica y Centro de Estudios en Diabetes, Morelos, Cuernavaca, Mexico; Instituto Nacional de Medicina Genómica, Mexico City, Mexico; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, United States; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 119228, Singapore; MRC Unit for Lifelong Health and Ageing at UCL, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom; Kurume University School of Medicine, Kurume, 830-0011, Japan; Genetics, Merck Sharp & Dohme Corp, Kenilworth, 07033, NJ, United States; Division of Population Health and Genomics, University of Dundee, Ninwells Hospital and Medical School, Dundee, DD1 9SY, United Kingdom; Intramural Research Program, National Institute on Aging, 3001 S. Hanover St., Baltimore, 21225, MD, United States; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Zhejiang, Wenzhou, 325027, China; Synlab Academy, SYNLAB Holding Deutschland GmbH, Mannheim and Augsburg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland; Leiden University Medical Center, Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden, 2333ZA, Netherlands; Amsterdam UMC, Department of General Practice and Elderly Care, Amsterdam Public Health Research Institute, Amsterdam, 1081HV, Netherlands; Department of Genetics, University of Pennsylvania, Philadelphia, 19104, PA, United States; Corporal Michael Crescenz VA Medical Center, Philadelphia, 19104, PA, United States; Institute of Social and Economic Research, University of Essex, Wivenhoe Park, CO4 3SQ, United Kingdom; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Department of Health Services, University of Washington, Seattle, WA, United States; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; 16Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, 12 South Drive, Room 4047, Bethesda, 20892, MD, United States; Danish Aging Research Center, University of Southern Denmark, Odense C, Denmark; Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Broad Institute of MIT and Harvard, Cambridge, MA, United States; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, 19104, PA, United States; Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, PA, United States; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, 19104, PA, United States; School of Medicine, Southern University of Science and Technology, Shenzhen, China; Netherlands Heart Institute, Utrecht, Netherlands; Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States; Department of Medicine, Harvard Medical School, Boston, MA, United States; Northern Finland Birth Cohorts, Infrastructure for population studies, Faculty of Medicine, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Biocenter of Oulu, University of Oulu, Oulu, Finland; Institute for Genetic and Biomedical Research, Italian National Council of Research (IRGB CNR), Cagliari, Italy; University of Sassari, Sassari, Italy; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands; Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Population Health Research Institute, St George's, University of London, London, SW17 0RE, United Kingdom; National Heart and Lung Institute, Imperial College London, London, W2 1PG, United Kingdom; School of Public Health, Imperial College London, London, W12 7RH, United Kingdom; Taichung Veterans General Hospital, Taichung, Taiwan; No. 1650, Sec. 4, Taiwan Boulevard, Xitun District Taichung City, 40705, Taiwan; Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, 112201, Taiwan; OCDEM, University of Oxford, Churchill Hospital, Oxford, OX3 7LE, United Kingdom; NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom; Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore; Data Science, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore; German Center for Diabetes Research (DZD), Neuherberg, Germany; University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, United Kingdom; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Framingham Heart Study, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, MD, United States; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, 201203, China; Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine, Munich, Germany; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; Stanford Cardiovascular Institute, Stanford University, Stanford, 94305, CA, United States; Stanford Diabetes Research Center, Stanford University, Stanford, 94305, CA, United States; Regeneron Pharmaceuticals, Tarrytown, NY, United States; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore; MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, United Kingdom; School of Electrical & Information Engineering, University of the Witwatersrand, Witwatersrand, South Africa; Institute for Minority Health Research, University of Illinois College of Medicine, Chicago, IL, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, 02115, MA, United States; QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, 4006, QLD, Australia; Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States; Department of Cardiology, Columbia University Irving Medical Center, New York, NY, United States; Big Data Instutute, University of Oxford, Oxford, OX3 7LF, United Kingdom; Aberdeen Centre for Health Data Science, 1:042 Polwarth Building School of Medicine, Medical Science and Nutrition University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom; Biomedical and Translational Informatics, Geisinger Health, Danville, 17822, PA, United States; School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States; Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, United States; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, United States; Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, 60611, IL, United States; Department of Anthropology, Northwestern University, Evanston, 60208, IL, United States; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, 7600, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, 7600, Norway; Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan; Laboratory of Statistical Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan; Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea; VA Boston Healthcare System, Boston, MA, United States; VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, United States; University of Massachusetts, Boston, MA, United States; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States; Department of Medicine, Brigham Women's Hospital, Boston, MA, United States; Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States; Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, United States; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia; Department of Human Genetics, University of Michigan, Ann Arbor, 48109, MI, United States; Department of Statistics, The Pennsylvania State University, University Park, PA, United States; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States; Department of Statistics, Stanford University, Stanford, CA, United States
