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      Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

      research-article
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      Nature
      Nature Publishing Group UK
      Diabetes, Genome-wide association studies, Computational biology and bioinformatics, Genetic markers

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          Abstract

          Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes 1, 2 and molecular mechanisms that are often specific to cell type 3, 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 scores 5 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.

          Abstract

          A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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          Most cited references67

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          • Abstract: found
          • Article: found
          Is Open Access

          A global reference for human genetic variation

          The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
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            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Second-generation PLINK: rising to the challenge of larger and richer datasets

            PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.
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              • Abstract: found
              • Article: found

              LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.

              Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.
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                Author and article information

                Contributors
                konstantinos.hatzikotoulas@helmholtz-munich.de
                bvoight28@gmail.com
                andrew.morris-5@manchester.ac.uk
                eleftheria.zeggini@helmholtz-munich.de
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                19 February 2024
                19 February 2024
                2024
                : 627
                : 8003
                : 347-357
                Affiliations
                [1 ]Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, ( https://ror.org/027m9bs27) Manchester, UK
                [2 ]Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, ( https://ror.org/057zh3y96) Tokyo, Japan
                [3 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Statistical Genetics, , Osaka University Graduate School of Medicine, ; Suita, Japan
                [4 ]Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Neuherberg, Germany
                [5 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Center for Precision Health Research, National Human Genome Research Institute, , National Institutes of Health, ; Bethesda, MD USA
                [6 ]British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, ( https://ror.org/013meh722) Cambridge, UK
                [7 ]Heart and Lung Research Institute, University of Cambridge, ( https://ror.org/013meh722) Cambridge, UK
                [8 ]Department of Epidemiology, School of Public Health, Nanjing Medical University, ( https://ror.org/059gcgy73) Nanjing, China
                [9 ]Department of Biostatistics and Center for Statistical Genetics, University of Michigan, ( https://ror.org/00jmfr291) Ann Arbor, MI USA
                [10 ]Corporal Michael J. Crescenz VA Medical Center, ( https://ror.org/03j05zz84) Philadelphia, PA USA
                [11 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Systems Pharmacology and Translational Therapeutics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [12 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Genetics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [13 ]Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, ( https://ror.org/05a0ya142) Cambridge, MA USA
                [14 ]Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, ( https://ror.org/002pd6e78) Boston, MA USA
                [15 ]GRID grid.38142.3c, ISNI 000000041936754X, TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, , Harvard Medical School, ; Boston, MA USA
                [16 ]GRID grid.4868.2, ISNI 0000 0001 2171 1133, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, , Queen Mary University of London, ; London, UK
                [17 ]Graduate School of Experimental Medicine, Technical University of Munich, ( https://ror.org/02kkvpp62) Munich, Germany
                [18 ]Munich School for Data Science, Helmholtz Munich, Neuherberg, Germany
                [19 ]Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, ( https://ror.org/057zh3y96) Tokyo, Japan
                [20 ]Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, ( https://ror.org/035t8zc32) Suita, Japan
                [21 ]Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, ( https://ror.org/04mb6s476) Yokohama, Japan
                [22 ]Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, ( https://ror.org/04a9tmd77) New York, NY USA
                [23 ]Department of Medicine, Vanderbilt University Medical Center, ( https://ror.org/05dq2gs74) Nashville, TN USA
                [24 ]Estonian Genome Centre, Institute of Genomics, University of Tartu, ( https://ror.org/03z77qz90) Tartu, Estonia
                [25 ]Nuffield Department of Population Health, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK
                [26 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Medical Research Council Population Health Research Unit, , University of Oxford, ; Oxford, UK
                [27 ]Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, ( https://ror.org/025j2nd68) Torrance, CA USA
                [28 ]Department of Epidemiology and Biostatistics, Imperial College London, ( https://ror.org/041kmwe10) London, UK
                [29 ]GRID grid.451052.7, ISNI 0000 0004 0581 2008, Department of Cardiology, Ealing Hospital, , London NorthWest Healthcare NHS Trust, ; London, UK
                [30 ]Division of Genome Science, Department of Precision Medicine, National Institute of Health, ( https://ror.org/00qdsfq65) Cheongju-si, South Korea
                [31 ]Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, ( https://ror.org/0130frc33) Chapel Hill, NC USA
                [32 ]Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, ( https://ror.org/00r9w3j27) Tokyo, Japan
                [33 ]Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Neuherberg, Germany
                [34 ]Department of Medicine, McMaster University, ( https://ror.org/02fa3aq29) Hamilton, Ontario Canada
                [35 ]GRID grid.413615.4, ISNI 0000 0004 0408 1354, Population Health Research Institute, , Hamilton Health Sciences and McMaster University, ; Hamilton, Ontario Canada
                [36 ]GRID grid.27476.30, ISNI 0000 0001 0943 978X, Public Health Informatics Unit, Department of Integrated Health Sciences, , Nagoya University Graduate School of Medicine, ; Nagoya, Japan
                [37 ]GRID grid.5335.0, ISNI 0000000121885934, MRC Epidemiology Unit, Institute of Metabolic Science, , University of Cambridge School of Clinical Medicine, ; Cambridge, UK
                [38 ]Department of Health Data Science, University of Liverpool, ( https://ror.org/04xs57h96) Liverpool, UK
                [39 ]Division of Translational Medicine and Human Genetics, University of Pennsylvania, ( https://ror.org/00b30xv10) Philadelphia, PA USA
                [40 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Epidemiology, , Brown University School of Public Health, ; Providence, RI USA
                [41 ]Department of Anthropology, University of Toronto at Mississauga, ( https://ror.org/03dbr7087) Mississauga, Ontario Canada
                [42 ]Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, ( https://ror.org/01tgyzw49) Singapore, Singapore
                [43 ]Department of Epidemiology, School of Public Health, University of Michigan, ( https://ror.org/00jmfr291) Ann Arbor, MI USA
                [44 ]Center for Genomic Medicine, Kyoto University Graduate School of Medicine, ( https://ror.org/02kpeqv85) Kyoto, Japan
                [45 ]deCODE Genetics, Amgen, ( https://ror.org/04dzdm737) Reykjavik, Iceland
                [46 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [47 ]Department of Biostatistics, Harvard University, ( https://ror.org/03vek6s52) Boston, MA USA
                [48 ]Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, ( https://ror.org/04b6nzv94) Boston, MA USA
                [49 ]Department of Medicine, Harvard University, ( https://ror.org/03vek6s52) Boston, MA USA
                [50 ]Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Center, University of Freiburg, ( https://ror.org/0245cg223) Freiburg, Germany
                [51 ]Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston School of Public Health, ( https://ror.org/03gds6c39) Houston, TX USA
                [52 ]German Center for Diabetes Research (DZD), ( https://ror.org/04qq88z54) Neuherberg, Germany
                [53 ]Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Neuherberg, Germany
                [54 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Department of Population and Public Health Sciences, , Keck School of Medicine of USC, ; Los Angeles, CA USA
                [55 ]Department of Cardiology, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [56 ]Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [57 ]Department of Internal Medicine, Seoul National University Hospital, ( https://ror.org/01z4nnt86) Seoul, South Korea
                [58 ]Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, ( https://ror.org/05dq2gs74) Nashville, TN USA
                [59 ]Nuffield Department of Surgical Sciences, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK
                [60 ]Institute for Population and Precision Health (IPPH), Biological Sciences Division, University of Chicago, ( https://ror.org/024mw5h28) Chicago, IL USA
                [61 ]Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, ( https://ror.org/0153tk833) Charlottesville, VA USA
                [62 ]GRID grid.417634.3, ISNI 0000 0004 0496 8123, Genomic Research on Complex Diseases (GRC-Group), , CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), ; Hyderabad, India
                [63 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Medicine and Therapeutics, , Chinese University of Hong Kong, ; Hong Kong, China
                [64 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, 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, China
                [65 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), , Sungkyunkwan University, Samsung Medical Center, ; Seoul, South Korea
                [66 ]Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA
                [67 ]Institute of Biomedical Sciences, Academia Sinica, ( https://ror.org/05bxb3784) Taipei, Taiwan
                [68 ]Department of Genetics, University of North Carolina at Chapel Hill, ( https://ror.org/0130frc33) Chapel Hill, NC USA
                [69 ]Department of Human Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, ( https://ror.org/05cy4wa09) Hinxton, UK
                [70 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Laboratory of Neurogenetics, National Institute on Aging, , National Institutes of Health, ; Bethesda, MD USA
                [71 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Medicine, , Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                [72 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Center for Research on Genomics and Global Health, National Human Genome Research Institute, , National Institutes of Health, ; Bethesda, MD USA
                [73 ]Cardiovascular Health Research Unit, Department of Medicine, University of Washington, ( https://ror.org/00cvxb145) Seattle, WA USA
                [74 ]GRID grid.416735.2, ISNI 0000 0001 0229 4979, Division of Academics, , Ochsner Health, ; New Orleans, LA USA
                [75 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Division of Statistical Genomics, , Washington University School of Medicine, ; St Louis, MO USA
                [76 ]GRID grid.280062.e, ISNI 0000 0000 9957 7758, Department of Research and Evaluation, Division of Biostatistics Research, , Kaiser Permanente of Southern California, ; Pasadena, CA USA
                [77 ]Department of Biomedical Science, Hallym University, ( https://ror.org/03sbhge02) Chuncheon, South Korea
                [78 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard Medical School, ; Boston, MA USA
                [79 ]GRID grid.5335.0, ISNI 0000000121885934, Metabolic Research Laboratories, Wellcome Trust–Medical Research Council Institute of Metabolic Science, Department of Clinical Biochemistry, , University of Cambridge, ; Cambridge, UK
                [80 ]GRID grid.4494.d, ISNI 0000 0000 9558 4598, Department of Epidemiology, University of Groningen, , University Medical Centre Groningen, ; Groningen, The Netherlands
                [81 ]Department of Bioinformatics, Isfahan University of Medical Sciences, ( https://ror.org/04waqzz56) Isfahan, Iran
                [82 ]Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, ( https://ror.org/02pammg90) Los Angeles, CA USA
                [83 ]GRID grid.411843.b, ISNI 0000 0004 0623 9987, Lund University Diabetes Centre, Department of Clinical Sciences, , Lund University, Skåne University Hospital, ; Malmö, Sweden
                [84 ]Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, ( https://ror.org/0130frc33) Chapel Hill, NC USA
                [85 ]Unidad de Investigación en Enfermedades Metabólicas and Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, ( https://ror.org/00xgvev73) Mexico City, Mexico
                [86 ]GRID grid.419658.7, ISNI 0000 0004 0646 7285, Steno Diabetes Center Copenhagen, ; Herlev, Denmark
                [87 ]Bioinformatics Center, Department of Biology, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                [88 ]Department of Health Research Methods, Evidence and Impact, McMaster University, ( https://ror.org/02fa3aq29) Hamilton, Ontario Canada
                [89 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Epidemiology and Prevention, Division of Public Health Sciences, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [90 ]Institute of Regional Health Research, University of Southern Denmark, ( https://ror.org/03yrrjy16) Odense, Denmark
                [91 ]Department of Clinical Biochemistry, Vejle Hospital, ( https://ror.org/00e8ar137) Vejle, Denmark
                [92 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Department of Medicine, Division of Endocrinology and Diabetes, , Keck School of Medicine of USC, ; Los Angeles, CA USA
                [93 ]Department of Internal Medicine, University of Michigan, ( https://ror.org/00jmfr291) Ann Arbor, MI USA
                [94 ]GRID grid.5335.0, ISNI 0000000121885934, British Heart Foundation Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, , University of Cambridge, ; Cambridge, UK
                [95 ]Health Data Research UK Cambridge, Wellcome Genome Campus, University of Cambridge, ( https://ror.org/013meh722) Hinxton, UK
                [96 ]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, ( https://ror.org/013meh722) Cambridge, UK
                [97 ]GRID grid.410463.4, ISNI 0000 0004 0471 8845, Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, ; Lille, France
                [98 ]University of Lille, ( https://ror.org/02kzqn938) Lille, France
                [99 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Li Ka Shing Institute of Health Sciences, , Chinese University of Hong Kong, ; Hong Kong, China
                [100 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Hong Kong Institute of Diabetes and Obesity, , Chinese University of Hong Kong, ; Hong Kong, China
                [101 ]GRID grid.419272.b, ISNI 0000 0000 9960 1711, Singapore Eye Research Institute, , Singapore National Eye Centre, ; Singapore, Singapore
                [102 ]Exeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, ( https://ror.org/03yghzc09) Exeter, UK
                [103 ]Wellcome Sanger Institute, Wellcome Genome Campus, ( https://ror.org/05cy4wa09) Hinxton, UK
                [104 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Biostatistics and Data Science, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [105 ]Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, ( https://ror.org/03nteze27) Taipei, Taiwan
                [106 ]Institute of Epidemiology and Preventive Medicine, National Taiwan University, ( https://ror.org/05bqach95) Taipei, Taiwan
                [107 ]Department of Medicine, University of Vermont, ( https://ror.org/0155zta11) Colchester, VT USA
                [108 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Section of Endocrinology and Metabolism, Department of Internal Medicine, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [109 ]Department of Medicine, Faculty of Medicine, University of Kelaniya, ( https://ror.org/02r91my29) Ragama, Sri Lanka
                [110 ]Department of Nutrition and Dietetics, Harokopio University of Athens, ( https://ror.org/02k5gp281) Athens, Greece
                [111 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Center for Genomics and Personalized Medicine Research, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [112 ]Carolina Population Center, University of North Carolina at Chapel Hill, ( https://ror.org/0130frc33) Chapel Hill, NC USA
                [113 ]Department of Nephrology and Medical Intensive Care Medicine, Charité–Universitätsmedizin Berlin, ( https://ror.org/001w7jn25) Berlin, Germany
                [114 ]Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, ( https://ror.org/00f7hpc57) Erlangen, Germany
                [115 ]Department of Biostatistics, University of Washington, ( https://ror.org/00cvxb145) Seattle, WA USA
                [116 ]California Pacific Medical Center Research Institute, ( https://ror.org/02bjh0167) San Francisco, CA USA
                [117 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, , National Institutes of Health, ; Baltimore, MD USA
                [118 ]Institute of Mathematics and Statistics, University of Tartu, ( https://ror.org/03z77qz90) Tartu, Estonia
                [119 ]Robertson Centre for Biostatistics, University of Glasgow, ( https://ror.org/00vtgdb53) Glasgow, UK
                [120 ]Department of Epidemiology, Erasmus MC University Medical Center, ( https://ror.org/018906e22) Rotterdam, The Netherlands
                [121 ]Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, ( https://ror.org/03yghzc09) Exeter, UK
                [122 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Internal Medicine, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [123 ]GRID grid.239844.0, ISNI 0000 0001 0157 6501, Department of Medicine, Division of Endocrinology and Metabolism, , Lundquist Research Institute at Harbor-UCLA Medical Center, ; Torrance, CA USA
                [124 ]Department of Public Health and Caring Sciences, Uppsala University, ( https://ror.org/048a87296) Uppsala, Sweden
                [125 ]Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, ( https://ror.org/032y0n460) Mexico City, Mexico
                [126 ]Department of Laboratory Medicine and Pathology, University of Minnesota, ( https://ror.org/017zqws13) Minneapolis, MN USA
                [127 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Genomics and Computational Biology Graduate Group, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [128 ]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Institute for Molecular Medicine Finland (FIMM), , University of Helsinki, ; Helsinki, Finland
                [129 ]GRID grid.428673.c, ISNI 0000 0004 0409 6302, Folkhalsan Research Center, ; Helsinki, Finland
                [130 ]University of Exeter Medical School, University of Exeter, ( https://ror.org/03yghzc09) Exeter, UK
                [131 ]GRID grid.429051.b, ISNI 0000 0004 0492 602X, Institute for Clinical Diabetology, German Diabetes Center, , Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, ; Düsseldorf, Germany
                [132 ]Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, ( https://ror.org/024z2rq82) Düsseldorf, Germany
                [133 ]Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, ( https://ror.org/04mb6s476) Yokohama, Japan
                [134 ]Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, ( https://ror.org/0130frc33) Chapel Hill, NC USA
                [135 ]Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center, ( https://ror.org/00c01js51) Columbus, OH USA
                [136 ]Center for Global Cardiometabolic Health, Brown University, ( https://ror.org/05gq02987) Providence, RI USA
                [137 ]Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
                [138 ]Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, ( https://ror.org/046h7rx26) Taipei, Taiwan
                [139 ]School of Medicine, National Defense Medical Center, ( https://ror.org/02bn97g32) Taipei, Taiwan
                [140 ]Division of Genome Science, Department of Precision Medicine, National Institute of Health, ( https://ror.org/00qdsfq65) Cheongju-si, Korea
                [141 ]Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, ( https://ror.org/03ymy8z76) Taipei, Taiwan
                [142 ]School of Medicine, National Yang Ming Chiao Tung University, ( https://ror.org/00se2k293) Taipei, Taiwan
                [143 ]Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, ( https://ror.org/010hz0g26) Shimotsuke, Japan
                [144 ]University of Chicago Research Bangladesh, ( https://ror.org/04bzg5466) Dhaka, Bangladesh
                [145 ]Institute of Molecular and Clinical Ophthalmology Basel, ( https://ror.org/05e715194) Basel, Switzerland
                [146 ]GRID grid.512917.9, Center for Clinical Research and Prevention, , Bispebjerg and Frederiksberg Hospital, ; Frederiksberg, Denmark
                [147 ]Faculty of Health and Medical Sciences, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                [148 ]Faculty of Medicine, Aalborg University, ( https://ror.org/04m5j1k67) Aalborg, Denmark
                [149 ]Department of Clinical Diabetes, Endocrinology and Metabolism, Department of Translational Research and Cellular Therapeutics, City of Hope, ( https://ror.org/00w6g5w60) Duarte, CA USA
                [150 ]Department of Public Health, Faculty of Medicine, University of Kelaniya, ( https://ror.org/02r91my29) Ragama, Sri Lanka
                [151 ]Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, ( https://ror.org/035t8zc32) Osaka, Japan
                [152 ]Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, ( https://ror.org/035t8zc32) Osaka, Japan
                [153 ]Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA
                [154 ]Center for Health Information Partnerships, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA
                [155 ]Genome Institute of Singapore, Agency for Science, Technology and Research, ( https://ror.org/05k8wg936) Singapore, Singapore
                [156 ]Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, ( https://ror.org/04q78tk20) Suwon, South Korea
                [157 ]GRID grid.5361.1, ISNI 0000 0000 8853 2677, Institute of Genetic Epidemiology, , Medical University of Innsbruck, ; Innsbruck, Austria
                [158 ]Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, ( https://ror.org/00fqdfs68) Kuopio, Finland
                [159 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Medicine, , University of Colorado Denver, Anschutz Medical Campus, ; Aurora, CO USA
                [160 ]GRID grid.280807.5, ISNI 0000 0000 9555 3716, VA Salt Lake City Health Care System, ; Salt Lake City, UT USA
                [161 ]Department of Internal Medicine, University of Utah School of Medicine, ( https://ror.org/03r0ha626) Salt Lake City, UT USA
                [162 ]Soochunhyang Institute of Medi-bio Science and Division of Endocrinology, Department of Internal Medicine, Soochunhyang University College of Medicine, Cheonan, South Korea
                [163 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Department of Medicine, Samsung Medical Center, , Sungkyunkwan University School of Medicine, ; Seoul, South Korea
                [164 ]USC-Office of Population Studies Foundation, University of San Carlos, ( https://ror.org/041jw5813) Cebu City, Philippines
                [165 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Medicine, , Harvard Medical School, ; Boston, MA USA
                [166 ]Division of General Internal Medicine, Massachusetts General Hospital, ( https://ror.org/002pd6e78) Boston, MA USA
                [167 ]Department of Epidemiology and Biostatistics, School of Public Health, Peking University, ( https://ror.org/02v51f717) Beijing, China
                [168 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Peking University Center for Public Health and Epidemic Preparedness and Response, ; Beijing, China
                [169 ]Department of Clinical Epidemiology, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [170 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK
                [171 ]Program in Medical and Population Genetics, Broad Institute, ( https://ror.org/05a0ya142) Cambridge, MA USA
                [172 ]Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK
                [173 ]Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                [174 ]Department of Biostatistics, Boston University School of Public Health, ( https://ror.org/05qwgg493) Boston, MA USA
                [175 ]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, ( https://ror.org/01tgyzw49) Singapore, Singapore
                [176 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, McDonnell Genome Institute, , Washington University School of Medicine, ; St Louis, MO USA
                [177 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Medicine, Division of Genomics and Bioinformatics, , Washington University School of Medicine, ; St Louis, MO USA
                [178 ]Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston School of Public Health, ( https://ror.org/03gds6c39) Houston, TX USA
                [179 ]Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, ( https://ror.org/012a77v79) Malmö, Sweden
                [180 ]Department of Clinical Science, Center for Diabetes Research, University of Bergen, ( https://ror.org/03zga2b32) Bergen, Norway
                [181 ]Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, ( https://ror.org/02z1n9q24) Nishihara, Japan
                [182 ]Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, ( https://ror.org/02z1n9q24) Nishihara, Japan
                [183 ]Dromokaiteio Psychiatric Hospital, National and Kapodistrian University of Athens, ( https://ror.org/04gnjpq42) Athens, Greece
                [184 ]Academy of Scientific and Innovative Research (AcSIR), ( https://ror.org/053rcsq61) Ghaziabad, India
                [185 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, , University of Tokyo, ; Tokyo, Japan
                [186 ]Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Neuherberg, Germany
                [187 ]Institute of Human Genetics, Technical University Munich, ( https://ror.org/02kkvpp62) Munich, Germany
                [188 ]German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, ( https://ror.org/031t5w623) Munich, Germany
                [189 ]Usher Institute to the Population Health Sciences and Informatics, University of Edinburgh, ( https://ror.org/01nrxwf90) Edinburgh, UK
                [190 ]Department of Medicine and Pharmacology, New York Medical College, ( https://ror.org/03dkvy735) Valhalla, NY USA
                [191 ]Data Tecnica International, ( https://ror.org/001h41c24) Glen Echo, MD USA
                [192 ]Center for Alzheimer’s and Related Dementias, National Institutes of Health, ( https://ror.org/01cwqze88) Bethesda, MD USA
                [193 ]Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, ( https://ror.org/035t8zc32) Suita, Japan
                [194 ]Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, ( https://ror.org/035t8zc32) Suita, Japan
                [195 ]Instituto Nacional de Medicina Genómica, ( https://ror.org/01qjckx08) Mexico City, Mexico
                [196 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, ( https://ror.org/01an3r305) Pittsburgh, PA USA
                [197 ]GRID grid.17635.36, ISNI 0000000419368657, Division of Epidemiology and Community Health, School of Public Health, , University of Minnesota, ; Minneapolis, MN USA
                [198 ]Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität München, ( https://ror.org/05591te55) Munich, Germany
                [199 ]Department of Diabetes and Endocrinology, Nelson R. Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, ( https://ror.org/04qzfn040) Durban, South Africa
                [200 ]Academy of Scientific and Innovative Research, CSIR-Human Resource Development Campus, ( https://ror.org/053rcsq61) Ghaziabad, India
                [201 ]Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, ( https://ror.org/05ef28661) New Delhi, India
                [202 ]GRID grid.270240.3, ISNI 0000 0001 2180 1622, Fred Hutchinson Cancer Research Center, ; Seattle, WA USA
                [203 ]Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, ( https://ror.org/02j1m6098) Singapore, Singapore
                [204 ]Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, ( https://ror.org/01tgyzw49) Singapore, Singapore
                [205 ]School of Cardiovascular and Metabolic Health, University of Glasgow, ( https://ror.org/00vtgdb53) Glasgow, UK
                [206 ]Survey Research Center, Institute for Social Research, University of Michigan, ( https://ror.org/00jmfr291) Ann Arbor, MI USA
                [207 ]Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Neuherberg, Germany
                [208 ]GRID grid.410607.4, Institute for Medical Biostatistics, Epidemiology, and Informatics (IMBEI), , University Medical Center, Johannes Gutenberg University, ; Mainz, Germany
                [209 ]Chair of Genetic Epidemiology, Institute of Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, ( https://ror.org/05591te55) Munich, Germany
                [210 ]Faculty of Medicine, University of Iceland, ( https://ror.org/01db6h964) Reykjavik, Iceland
                [211 ]GRID grid.259384.1, ISNI 0000 0000 8945 4455, Faculty of Medicine, , Macau University of Science and Technology, ; Macau, China
                [212 ]Department of Medical Genetics and Medical Research, China Medical University Hospital, ( https://ror.org/0368s4g32) Taichung, Taiwan
                [213 ]Population Health Unit, Finnish Institute for Health and Welfare, ( https://ror.org/03tf0c761) Helsinki, Finland
                [214 ]National School of Public Health, ( https://ror.org/003xj6z62) Madrid, Spain
                [215 ]Department of Public Health, University of Helsinki, ( https://ror.org/040af2s02) Helsinki, Finland
                [216 ]Diabetes Research Group, King Abdulaziz University, ( https://ror.org/02ma4wv74) Jeddah, Saudi Arabia
                [217 ]Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, ( https://ror.org/00xgvev73) Mexico City, Mexico
                [218 ]GRID grid.9486.3, ISNI 0000 0001 2159 0001, Departamento de Medicina Genómica y Toxiología Ambiental, , Instituto de Investigaciones Biomédicas, UNAM, ; Mexico City, Mexico
                [219 ]GRID grid.419157.f, ISNI 0000 0001 1091 9430, Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, , Instituto Mexicano del Seguro Social, ; Mexico City, Mexico
                [220 ]Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [221 ]Department of Human Genetics, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [222 ]Department of Clinical Chemistry, Laboratory of Genetic Metabolic Disease, Amsterdam University Medical Center, ( https://ror.org/05grdyy37) Amsterdam, The Netherlands
                [223 ]Southern California Eye Institute, CHA Hollywood Presbyterian Hospital, ( https://ror.org/012mmb732) Los Angeles, CA USA
                [224 ]GRID grid.419157.f, ISNI 0000 0001 1091 9430, Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, , Instituto Mexicano del Seguro Social, ; Mexico City, Mexico
                [225 ]Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, ( https://ror.org/05xvt9f17) Leiden, The Netherlands
                [226 ]Department of Public Health, Aarhus University, ( https://ror.org/01aj84f44) Aarhus, Denmark
                [227 ]Danish Diabetes Academy, ( https://ror.org/05xbkrn90) Odense, Denmark
                [228 ]Diabetology Research Centre, King Edward Memorial Hospital and Research Centre, ( https://ror.org/056yyyw24) Pune, India
                [229 ]Department of Medical Biochemistry, Kurume University School of Medicine, ( https://ror.org/057xtrt18) Kurume, Japan
                [230 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Pediatrics, , Osaka University Graduate School of Medicine, ; Suita, Japan
                [231 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, , University of Pittsburgh, ; Pittsburgh, PA USA
                [232 ]Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, ( https://ror.org/01an3r305) Pittsburgh, PA USA
                [233 ]GRID grid.266093.8, ISNI 0000 0001 0668 7243, Department of Pediatrics, Division of Genetic and Genomic Medicine, , UCI Irvine School of Medicine, ; Irvine, CA USA
                [234 ]Department of Anti-Aging Medicine, Ehime University Graduate School of Medicine, ( https://ror.org/017hkng22) Touon, Japan
                [235 ]Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, ( https://ror.org/04drvxt59) Boston, MA USA
                [236 ]Department of Medical Sciences, Uppsala University, ( https://ror.org/048a87296) Uppsala, Sweden
                [237 ]Institute of Molecular Medicine, University of Texas Health Science Center at Houston School of Public Health, ( https://ror.org/03gds6c39) Houston, TX USA
                [238 ]GRID grid.267308.8, ISNI 0000 0000 9206 2401, Human Genetics Center, , University of Texas Health Science Center at Houston, ; Houston, TX USA
                [239 ]GRID grid.168010.e, ISNI 0000000419368956, Department of Medicine, , Stanford University School of Medicine, ; Stanford, CA USA
                [240 ]Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, ( https://ror.org/048a87296) Uppsala, Sweden
                [241 ]Department of Epidemiology, University of Washington, ( https://ror.org/00cvxb145) Seattle, WA USA
                [242 ]Department of Health Systems and Population Health, University of Washington, ( https://ror.org/00cvxb145) Seattle, WA USA
                [243 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, , Capital Medical University, ; Beijing, China
                [244 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Department of Medicine, Division of Cardiology, , Duke University School of Medicine, ; Durham, NC USA
                [245 ]Kurume University School of Medicine, ( https://ror.org/057xtrt18) Kurume, Japan
                [246 ]Department of Medicine, McGill University, ( https://ror.org/01pxwe438) Montreal, Quebec Canada
                [247 ]Department of Human Genetics, McGill University, ( https://ror.org/01pxwe438) Montreal, Quebec Canada
                [248 ]Department of Metabolism, Digestion and Reproduction, Imperial College London, ( https://ror.org/041kmwe10) London, UK
                [249 ]Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, ( https://ror.org/04drvxt59) Boston, MA USA
                [250 ]Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, ( https://ror.org/00e87hq62) Taichung, Taiwan
                [251 ]Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA
                [252 ]Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA
                [253 ]Department of Anthropology, Northwestern University, ( https://ror.org/000e0be47) Evanston, IL USA
                [254 ]Department of Endocrinology, Helsinki University Hospital, ( https://ror.org/02e8hzf44) Helsinki, Finland
                [255 ]GRID grid.454780.a, ISNI 0000 0001 0683 2228, Science and Engineering Research Board (SERB), Department of Science and Technology, Ministry of Science and Technology, , Government of India, ; New Delhi, India
                [256 ]Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, ( https://ror.org/0567v8t28) New Delhi, India
                [257 ]Department of Pathology and Molecular Medicine, McMaster University, ( https://ror.org/02fa3aq29) Hamilton, Ontario Canada
                [258 ]Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, ( https://ror.org/04h9pn542) Seoul, South Korea
                [259 ]Netherlands Heart Institute, ( https://ror.org/01mh6b283) Utrecht, The Netherlands
                [260 ]Center for Public Health Genomics, University of Virginia School of Medicine, ( https://ror.org/0153tk833) Charlottesville, VA USA
                [261 ]Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, ( https://ror.org/00cfam450) Munich, Germany
                [262 ]Duke-NUS Medical School, ( https://ror.org/02j1m6098) Singapore, Singapore
                [263 ]Department of Epidemiology, Biostatistics and Occupational Health, McGill University, ( https://ror.org/01pxwe438) Montreal, Quebec Canada
                [264 ]GRID grid.185448.4, ISNI 0000 0004 0637 0221, Singapore Institute for Clinical Sciences, , Agency for Science Technology and Research (A*STAR), ; Singapore, Singapore
                [265 ]Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, ( https://ror.org/01tgyzw49) Singapore, Singapore
                [266 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Center for Diabetes Research, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [267 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Biochemistry, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [268 ]Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, ( https://ror.org/03h2bxq36) Dundee, UK
                [269 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Imperial College Healthcare NHS Trust, , Imperial College London, ; London, UK
                [270 ]MRC-PHE Centre for Environment and Health, Imperial College London, ( https://ror.org/041kmwe10) London, UK
                [271 ]National Heart and Lung Institute, Imperial College London, ( https://ror.org/041kmwe10) London, UK
                [272 ]Department of Medicine, Brown University Alpert School of Medicine, ( https://ror.org/05gq02987) Providence, RI USA
                [273 ]Department of Medicine, Columbia University Irving Medical Center, ( https://ror.org/01esghr10) New York, NY USA
                [274 ]Department of Cardiology, Columbia University Irving Medical Center, ( https://ror.org/01esghr10) New York, NY USA
                [275 ]Center for Non-Communicable Diseases, ( https://ror.org/05xnw5k32) Karachi, Pakistan
                [276 ]GRID grid.484013.a, ISNI 0000 0004 6879 971X, Computational Medicine, , Berlin Institute of Health at Charité–Universitätsmedizin, ; Berlin, Germany
                [277 ]Precision Healthcare University Research Institute, Queen Mary University of London, ( https://ror.org/026zzn846) London, UK
                [278 ]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Department of Preventive Medicine, , Keck School of Medicine of USC, ; Los Angeles, CA USA
                [279 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, The Mindich Child Health and Development Institute, , Ichan School of Medicine at Mount Sinai, ; New York, NY USA
                [280 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Division of Translational Medicine and Therapeutics, Department of Medicine, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [281 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Institute for Translational Medicine and Therapeutics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [282 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Pediatrics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [283 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Center for Precision Medicine, , University of Pennsylvania - Perelman School of Medicine, ; Philadelphia, PA USA
                [284 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Institute for Biomedical Informatics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [285 ]Department of Psychiatry, University of Michigan, ( https://ror.org/00jmfr291) Ann Arbor, MI USA
                [286 ]Blizard Institute, Queen Mary University of London, ( https://ror.org/026zzn846) London, UK
                [287 ]Institute for Population Health Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, ( https://ror.org/026zzn846) London, UK
                [288 ]All of Us Research Program, National Institutes of Health, ( https://ror.org/01cwqze88) Bethesda, MD USA
                [289 ]Toranomon Hospital, ( https://ror.org/05rkz5e28) Tokyo, Japan
                [290 ]Lee Kong Chian School of Medicine, Nanyang Technological University, ( https://ror.org/02e7b5302) Singapore, Singapore
                [291 ]Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, ( https://ror.org/05dq2gs74) Nashville, TN USA
                [292 ]VA Palo Alto Health Care System, ( https://ror.org/00nr17z89) Palo Alto, CA USA
                [293 ]GRID grid.168010.e, ISNI 0000000419368956, Stanford Cardiovascular Institute, , Stanford University School of Medicine, ; Stanford, CA USA
                [294 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Medicine, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [295 ]Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, ( https://ror.org/052gg0110) Oxford, UK
                [296 ]GRID grid.410556.3, ISNI 0000 0001 0440 1440, Oxford NIHR Biomedical Research Centre, Churchill Hospital, , Oxford University Hospitals NHS Foundation Trust, ; Oxford, UK
                [297 ]Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, ( https://ror.org/0072zz521) Amherst, MA USA
                [298 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Biostatistics, Epidemiology and Informatics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [299 ]TUM School of Medicine and Health, Technical University of Munich and Klinikum Rechts der Isar, ( https://ror.org/04jc43x05) Munich, Germany
                [300 ]GRID grid.418961.3, ISNI 0000 0004 0472 2713, Present Address: Regeneron Genetics Center, ; Tarrytown, NY USA
                [301 ]Present Address: Genentech, ( https://ror.org/04gndp242) South San Francisco, CA USA
                Author information
                http://orcid.org/0000-0002-4699-3672
                http://orcid.org/0000-0003-2088-5240
                http://orcid.org/0000-0001-6454-2384
                http://orcid.org/0000-0001-8674-2942
                http://orcid.org/0000-0002-4393-0510
                http://orcid.org/0000-0001-5585-3420
                http://orcid.org/0000-0001-8494-3660
                http://orcid.org/0000-0002-6442-7754
                http://orcid.org/0000-0001-7191-1723
                http://orcid.org/0000-0003-4924-5714
                http://orcid.org/0000-0002-6205-9994
                http://orcid.org/0000-0002-6805-6014
                http://orcid.org/0000-0003-4238-659X
                Article
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                10.1038/s41586-024-07019-6
                10937372
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                © The Author(s) 2024

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                History
                : 22 March 2023
                : 3 January 2024
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                diabetes,genome-wide association studies,computational biology and bioinformatics,genetic markers

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