Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J. Taylor, Xianyong Yin, Kim M. Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E. M. Melloni, Stavroula Kanoni, Nigel W. Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S. K. Lee, Michael H. Preuss, Lauren E. Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A. Scott, James P. Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J. Parra, Jin-Fang Chai, Lawrence F. Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S. Nongmaithem, Raymond Noordam, Victor J. Y. Lim, Claudia H. T. Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M. Raffield, Bram Peter Prins, Aude Nicolas, Lisa R. Yanek, Guanjie Chen, Jennifer A. Brody, Edmond Kabagambe, Ping An, Anny H. Xiang, Hyeok Sun Choi, Brian E. Cade, Jingyi Tan, K. Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S. Adair, Adebowale Adeyemo, Carlos A. Aguilar-Salinas, Tarunveer S. Ahluwalia, Sonia S. Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A. Buchanan, Charles F. Burant, Adam S. Butterworth, Mickaël Canouil, Juliana C. N. Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K. Das, H. Janaka de Silva, George Dedoussis, Latchezar Dimitrov, Ayo P. Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S. Emery, Daniel S. Evans, Michele K. Evans, Krista Fischer, James S. Floyd, Ian Ford, Oscar H. Franco, Timothy M. Frayling, Barry I. Freedman, Pauline Genter, Hertzel C. Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A. Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T. Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B. Jonas, Torben Jørgensen, Frederick K. Kamanu, Fouad R. Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M. Keaton, Abel N. Kho, Chiea-Chuen Khor, Muhammad G. Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A. Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R. Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M. Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E. Locke, Tin Louie, Jian’an Luan, Andrea O. Luk, Xi Luo, Jun Lv, Julie A. Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D. Morris, Filipe A. Moura, Jerry L. Nadler, Michael A. Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R. Patel, Snehal Patil, Pei Pei, Mark A. Pereira, Annette Peters, Fraser J. Pirie, Hannah G. Polikowsky, Bianca Porneala, Gauri Prasad, Laura J. Rasmussen-Torvik, Alexander P. Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A. Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M. Stilp, Konstantin Strauch, Kent D. Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C. Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S. Udler, Adan Valladares-Salgado, Rob M. van Dam, Jan B. van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R. Wickremasinghe, Ko Willems van Dijk, Daniel R. Witte, Chittaranjan S. Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Stavroula Kanona, David A. van Heel, Leslie J. Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A. Province, Myriam Fornage, Craig L. Hanis, Erik Ingelsson, Alan B. Zonderman, Bruce M. Psaty, Ya-Xing Wang, Charles N. Rotimi, Diane M. Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L. R. Kardia, Patricia A. Peyser, James S. Pankow, James C. Engert, Amélie Bonnefond, Philippe Froguel, James G. Wilson, Wayne H. H. Sheu, Jer-Yuarn Wu, M. Geoffrey Hayes, Ronald C. W. Ma, Tien-Yin Wong, Dennis O. Mook-Kanamori, Tiinamaija Tuomi, Giriraj R. Chandak, Francis S. Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M. Sale, Habibul Ahsan, Ayesha A. Motala, Xiao-Ou Shu, Kyong-Soo Park, J. Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S. Rich, Roberta McKean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W. Bowden, Colin N. A. Palmer, Jaspal S. Kooner, Charles Kooperberg, Simin Liu, Kari E. North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J. Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y. Millwood, Robin G. Walters, Kari Stefansson, Emma Ahlqvist, Mark O. Goodarzi, Karen L. Mohlke, Claudia Langenberg, Christopher A. Haiman, Ruth J. F. Loos, Jose C. Florez, Daniel J. Rader, Marylyn D. Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A. Marston, Christian T. Ruff, Sarah Finer, Joshua C. Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C. Chambers, Maggie C. Y. Ng, Xueling Sim, Jennifer E. Below, Philip S. Tsao, Kyong-Mi Chang, Mark I. McCarthy, James B. Meigs, Anubha Mahajan, Cassandra N. Spracklen, Josep M. Mercader, Michael Boehnke, Jerome I. Rotter, Marijana Vujkovic, Benjamin F. Voight, Andrew P. Morris, Eleftheria Zeggini
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care. © The Author(s) 2024.
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Graduate School of Experimental Medicine, Technical University of Munich, Munich, Germany; Munich School for Data Science, Helmholtz Munich, Neuherberg, Germany; Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, United Kingdom; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Department of Cardiology, Ealing Hospital, London NorthWest Healthcare NHS Trust, London, United Kingdom; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine, McMaster University, Hamilton, ON, Canada; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom; Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, United States; Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States; Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; deCODE Genetics, Amgen, Reykjavik, Iceland; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biostatistics, Harvard University, Boston, MA, United States; Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, United States; Department of Medicine, Harvard University, Boston, MA, United States; Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States; German Center for Diabetes Research (DZD), Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA, United States; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Institute for Population and Precision Health (IPPH), Biological Sciences Division, University of Chicago, Chicago, IL, United States; Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States; Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; Chinese University of Hong Kong–Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong; Samsung Advanced Institute for Health Sciences & amp; Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States; Division of Academics, Ochsner Health, New Orleans, LA, United States; Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, United States; Department of Research and Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern California, Pasadena, CA, United States; Department of Biomedical Science, Hallym University, Chuncheon, South Korea; Harvard Medical School, Boston, MA, United States; Metabolic Research Laboratories, Wellcome Trust–Medical Research Council Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands; Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Unidad de Investigación en Enfermedades Metabólicas and Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Steno Diabetes Center Copenhagen, Herlev, Denmark; Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark; Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine of USC, Los Angeles, CA, United States; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom; Health Data Research UK Cambridge, University of Cambridge, Wellcome Genome Campus, Hinxton, United Kingdom; National Institute for Health and Care Research (NIHR) Blood and Transplant Unit (BTRU) in Donor Health and Behaviour, Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France; University of Lille, Lille, France; Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, Chinese University of Hong Kong, Hong Kong; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Exeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom; Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, United States; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Department of Medicine, University of Vermont, Colchester, VT, United States; Section of Endocrinology and Metabolism, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka; Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States; Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Nephrology and Medical Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Biostatistics, University of Washington, Seattle, WA, United States; California Pacific Medical Center Research Institute, San Francisco, CA, United States; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States; Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Medicine, Division of Endocrinology and Metabolism, Lundquist Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, Mexico City, Mexico; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States; Genomics and Computational Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Folkhalsan Research Center, Helsinki, Finland; University of Exeter Medical School, University of Exeter, Exeter, United Kingdom; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center, Columbus, OH, United States; Center for Global Cardiometabolic Health, Brown University, Providence, RI, United States; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China; Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; University of Chicago Research Bangladesh, Dhaka, Bangladesh; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Diabetes, Endocrinology and Metabolism, Department of Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, United States; Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Center for Health Information Partnerships, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea; Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States; VA Salt Lake City Health Care System, Salt Lake City, UT, United States; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States; Soochunhyang Institute of Medi-bio Science and Division of Endocrinology, Department of Internal Medicine, Soochunhyang University College of Medicine, Cheonan, South Korea; Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Department of Medicine, Harvard Medical School, Boston, MA, United States; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, United States; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United States; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom; 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 Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore; McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, United States; Department of Medicine, Division of Genomics and Bioinformatics, Washington University School of Medicine, St Louis, MO, United States; Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States; Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden; Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway; Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan; Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan; Dromokaiteio Psychiatric Hospital, National and Kapodistrian University of Athens, Athens, Greece; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India; Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan; Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technical University Munich, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Usher Institute to the Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY, United States; Data Tecnica International, Glen Echo, MD, United States; Center for Alzheimer’s and Related Dementias, National Institutes of Health, Bethesda, MD, United States; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan; Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Japan; Instituto Nacional de Medicina Genómica, Mexico City, Mexico; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States; Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Diabetes and Endocrinology, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Campus, Ghaziabad, India; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India; Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore; School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United States; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany; Institute for Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany; Chair of Genetic Epidemiology, Institute of Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, Macau University of Science and Technology, Macao; Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland; National School of Public Health, Madrid, Spain; Department of Public Health, University of Helsinki, Helsinki, Finland; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Departamento de Medicina Genómica y Toxiología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico; Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Department of Clinical Chemistry, Laboratory of Genetic Metabolic Disease, Amsterdam University Medical Center, Amsterdam, Netherlands; Southern California Eye Institute, CHA Hollywood Presbyterian Hospital, Los Angeles, CA, United States; Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands; Department of Public Health, Aarhus University, Aarhus, Denmark; Danish Diabetes Academy, Odense, Denmark; Diabetology Research Centre, King Edward Memorial Hospital and Research Centre, Pune, India; Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan; Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Department of Pediatrics, Division of Genetic and Genomic Medicine, UCI Irvine School of Medicine, Irvine, CA, United States; Department of Anti-Aging Medicine, Ehime University Graduate School of Medicine, Touon, Japan; Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States; Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Institute of Molecular Medicine, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, United States; Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, United States; Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Epidemiology, University of Washington, Seattle, WA, United States; Department of Health Systems and Population Health, University of Washington, Seattle, WA, United States; Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, United States; Kurume University School of Medicine, Kurume, Japan; Department of Medicine, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States; Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Department of Anthropology, Northwestern University, Evanston, IL, United States; Department of Endocrinology, Helsinki University Hospital, Helsinki, Finland; Science and Engineering Research Board (SERB), Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi, India; Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea; Netherlands Heart Institute, Utrecht, Netherlands; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany; Duke-NUS Medical School, Singapore, Singapore; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States; Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Dundee, United Kingdom; Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Medicine, Brown University Alpert School of Medicine, Providence, RI, United States; 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; Center for Non-Communicable Diseases, Karachi, Pakistan; Computational Medicine, Berlin Institute of Health at Charité–Universitätsmedizin, Berlin, Germany; Precision Healthcare University Research Institute, Queen Mary University of London, London, United Kingdom; Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States; The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, United States; Division of Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Center for Precision Medicine, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, United States; Institute for Biomedical Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States; Blizard Institute, Queen Mary University of London, London, United Kingdom; Institute for Population Health Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; All of Us Research Program, National Institutes of Health, Bethesda, MD, United States; Toranomon Hospital, Tokyo, Japan; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; VA Palo Alto Health Care System, Palo Alto, CA, United States; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, United States; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; TUM School of Medicine and Health, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany; Regeneron Genetics Center, Tarrytown, NY, United States; Genentech, South San Francisco, CA, United States
