3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Genetic diversity fuels gene discovery for tobacco and alcohol use

      research-article
      1 , 2 , 2 , 1 , 1 , 2 , 2 , 3 , 2 , 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 18 , 24 , 25 , 26 , 27 , 28 , 29 , 15 , 30 , 18 , 31 , 32 , 33 , 8 , 15 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 25 , 46 , 9 , 47 , 48 , 49 , 25 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 28 , 57 , 58 , 59 , 12 , 13 , 18 , 60 , 61 , 62 , 48 , 63 , 64 , 65 , 66 , 24 , 67 , 68 , 69 , 70 , 53 , 71 , 72 , 73 , 74 , 51 , 75 , 76 , 77 , 78 , 79 , 29 , 44 , 80 , 81 , 82 , 83 , 59 , 84 , 85 , 86 , 87 , 1 , 77 , 80 , 88 , 89 , 44 , 90 , 91 , 92 , 93 , 5 , 94 , 69 , 95 , 96 , 21 , 51 , 75 , 72 , 73 , 19 , 69 , 96 , 80 , 81 , 97 , 98 , 99 , 98 , 100 , 101 , 1 , 86 , 102 , 103 , 37 , 35 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 86 , 111 , 52 , 112 , 64 , 88 , 5 , 113 , 114 , 1 , 115 , 104 , 53 , 26 , 35 , 36 , 114 , 116 , 117 , 39 , 40 , 114 , 28 , 56 , 59 , 118 , 93 , 17 , 119 , 120 , 121 , 122 , 56 , 30 , 96 , 103 , 123 , 69 , 124 , 125 , 126 , 127 , 21 , 128 , 129 , 15 , 31 , 32 , 130 , 131 , 69 , 124 , 132 , 112 , 78 , 133 , 68 , 31 , 134 , 65 , 135 , 136 , 137 , 138 , 138 , 133 , 59 , 21 , 54 , 124 , 139 , 140 , 18 , 141 , 51 , 75 , 24 , 24 , 142 , 51 , 72 , 1 , 143 , 144 , 145 , 146 , 68 , 12 , 41 , 147 , 80 , 81 , 134 , 148 , 35 , 36 , 54 , 100 , 149 , 64 , 150 , 29 , 151 , 152 , 153 , 59 , 154 , 155 , 114 , 20 , 41 , 156 , 78 , 28 , 21 , 153 , 157 , 158 , 159 , 144 , 146 , 160 , 23andMe Research Team, The Biobank Japan Project, 161 , 162 , 163 , 132 , 164 , 165 , 166 , 167 , 168 , 88 , 2 , 144 , 145 , 169 , 24 , 2 , , 1 ,
      Nature
      Nature Publishing Group UK
      Genome-wide association studies, Risk factors, Human behaviour

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury 14 . These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries 5 . Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

          Abstract

          A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

          Related collections

          Most cited references59

          • Record: found
          • 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.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The UK Biobank resource with deep phenotyping and genomic data

            The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found
              Is Open Access

              The Genotype-Tissue Expression (GTEx) project.

              Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
                Bookmark

                Author and article information

                Contributors
                dajiang.liu@psu.edu
                vrieze@umn.edu
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                7 December 2022
                7 December 2022
                2022
                : 612
                : 7941
                : 720-724
                Affiliations
                [1 ]GRID grid.17635.36, ISNI 0000000419368657, Department of Psychology, , University of Minnesota, ; Minneapolis, MN USA
                [2 ]GRID grid.240473.6, ISNI 0000 0004 0543 9901, Department of Public Health Sciences, , Penn State College of Medicine, ; Hershey, PA USA
                [3 ]GRID grid.168010.e, ISNI 0000000419368956, Department of Epidemiology & Population Health at Stanford University, ; Stanford, CA USA
                [4 ]GRID grid.257990.0, ISNI 0000 0001 0671 8898, Jackson Heart Study (JHS) Graduate Training and Education Center (GTEC), Department of Epidemiology and Biostatistics, School of Public Health, , Jackson State University, ; Jackson, MS USA
                [5 ]GRID grid.509459.4, ISNI 0000 0004 0472 0267, Laboratory for Statistical and Translational Genetics, , RIKEN Center for Integrative Medical Sciences, ; Yokohama, Japan
                [6 ]GRID grid.177174.3, ISNI 0000 0001 2242 4849, Department of Ocular Pathology and Imaging Science, , Kyushu University Graduate School of Medical Sciences, ; Fukuoka, Japan
                [7 ]GRID grid.50956.3f, ISNI 0000 0001 2152 9905, Smidt Heart Institute, , Cedars-Sinai Medical Center, ; Los Angeles, CA USA
                [8 ]GRID grid.38142.3c, ISNI 000000041936754X, Division of Preventive Medicine, , Brigham and Women’s Hospital and Harvard Medical School, ; Boston, MA USA
                [9 ]GRID grid.430387.b, ISNI 0000 0004 1936 8796, Department of Psychiatry, , Rutgers Robert Wood Johnson Medical School, ; New Brunswick, NJ USA
                [10 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Epidemiology, Rollins School of Public Health, , Emory University, ; Atlanta, GA USA
                [11 ]GRID grid.266539.d, ISNI 0000 0004 1936 8438, Dean’s Office and Department of Epidemiology, , College of Public Health, University of Kentucky, ; Lexington, KY USA
                [12 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Department of Medicine and Duke Comprehensive Sickle Cell Center, , Duke University School of Medicine, ; Durham, NC USA
                [13 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Duke Molecular Physiology Institute, , Duke University School of Medicine, ; Durham, NC USA
                [14 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Division of Hematology, Department of Medicine, , Mayo Clinic College of Medicine and Science, ; Rochester, MN USA
                [15 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Division of Biomedical Informatics & Personalized Medicine, , University of Colorado Anschutz Medical Campus, ; Aurora, CO USA
                [16 ]GRID grid.511425.6, ISNI 0000 0004 9346 3636, Tempus, ; Chicago, IL USA
                [17 ]GRID grid.239585.0, ISNI 0000 0001 2285 2675, Department of Medicine, , Columbia University Medical Center, ; New York, NY USA
                [18 ]GRID grid.34477.33, ISNI 0000000122986657, Cardiovascular Health Research Unit, Department of Medicine, , University of Washington, ; Seattle, WA USA
                [19 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Biostatistics, , University of Washington, ; Seattle, WA USA
                [20 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Medicine, , Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                [21 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Epidemiology, School of Public Health, , University of Michigan, ; Ann Arbor, MI USA
                [22 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Medicine, Boston Medical Center, , Boston University School of Medicine, ; Boston, MA USA
                [23 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Epidemiology, , Boston University School of Public Health, ; Boston, MA USA
                [24 ]GRID grid.421812.c, ISNI 0000 0004 0618 6889, deCODE Genetics/Amgen, Inc., ; Reykjavik, Iceland
                [25 ]GRID grid.449717.8, ISNI 0000 0004 5374 269X, Department of Human Genetics and South Texas Diabetes and Obesity Institute, , University of Texas Rio Grande Valley School of Medicine, ; Brownsville, TX USA
                [26 ]GRID grid.134563.6, ISNI 0000 0001 2168 186X, Department of Medicine, , University of Arizona, ; Tucson, AZ USA
                [27 ]GRID grid.266190.a, ISNI 0000000096214564, Institute of Behavioral Science, , University of Colorado Boulder, ; Boulder, CO USA
                [28 ]GRID grid.267308.8, ISNI 0000 0000 9206 2401, Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, , The University of Texas Health Science Center at Houston, ; Houston, TX USA
                [29 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Netherlands Twin Register, Dept Biological Psychology, , Vrije Universiteit Amsterdam, ; Amsterdam, The Netherlands
                [30 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Biochemistry, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [31 ]GRID grid.62560.37, ISNI 0000 0004 0378 8294, Division of Sleep and Circadian Disorders, , Brigham and Women’s Hospital, ; Boston, MA USA
                [32 ]GRID grid.38142.3c, ISNI 000000041936754X, Division of Sleep Medicine, , Harvard Medical School, ; Boston, MA USA
                [33 ]GRID grid.66859.34, ISNI 0000 0004 0546 1623, Program in Medical and Population Genetics, , Broad Institute, ; Cambridge, MA USA
                [34 ]GRID grid.513199.6, Institute for Translational Genomics and Population Sciences, Department of Pediatrics, , Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, ; Torrance, CA USA
                [35 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK
                [36 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, MRC Population Health Research Unit, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK
                [37 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Epidemiology & Biostatistics, , University of California, ; San Francisco, CA USA
                [38 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, UCSF Helen Diller Family Comprehensive Cancer Center, , University of California, ; San Francisco, CA USA
                [39 ]GRID grid.62560.37, ISNI 0000 0004 0378 8294, Channing Division of Network Medicine, Department of Medicine, , Brigham and Women’s Hospital, ; Boston, MA USA
                [40 ]GRID grid.62560.37, ISNI 0000 0004 0378 8294, Division of Pulmonary and Critical Care Medicine, Department of Medicine, , Brigham and Women’s Hospital, ; Boston, MA USA
                [41 ]GRID grid.280062.e, ISNI 0000 0000 9957 7758, Kaiser Permanente Northern California (KPNC), , Division of Research, ; Oakland, CA USA
                [42 ]GRID grid.280711.d, ISNI 0000 0004 0419 6661, Department of Neurology, , Baltimore Veterans Affairs Medical Center, ; Baltimore, MD USA
                [43 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Division of Vascular Neurology, Department of Neurology, , University of Maryland School of Medicine, ; Baltimore, MD USA
                [44 ]GRID grid.16753.36, ISNI 0000 0001 2299 3507, Department of Preventive Medicine, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
                [45 ]GRID grid.11450.31, ISNI 0000 0001 2097 9138, University of Sassari, ; Sassari SS, Italy
                [46 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, , Mayo Clinic College of Medicine and Science, ; Rochester, MN USA
                [47 ]GRID grid.223827.e, ISNI 0000 0001 2193 0096, Department of Psychiatry, , University of Utah School of Medicine, ; Salt Lake City, UT USA
                [48 ]GRID grid.224260.0, ISNI 0000 0004 0458 8737, Virginia Institute for Psychiatric and Behavioral Genetics, , Virginia Commonwealth University, ; Virginia, USA
                [49 ]Huntsman Mental Health Institute, Salt Lake City, UT USA
                [50 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Family Medicine, , Brown University, ; Providence, RI USA
                [51 ]GRID grid.266190.a, ISNI 0000000096214564, Institute for Behavioral Genetics, , University of Colorado Boulder, ; Boulder, CO USA
                [52 ]GRID grid.266190.a, ISNI 0000000096214564, Department of Integrative Physiology, , University of Colorado Boulder, ; Boulder, CO USA
                [53 ]GRID grid.10939.32, ISNI 0000 0001 0943 7661, Institute of Genomics, , University of Tartu, ; Tartu, Estonia
                [54 ]GRID grid.214458.e, ISNI 0000000086837370, Survey Research Center, Institute for Social Research, , University of Michigan, ; Ann Arbor, MI USA
                [55 ]GRID grid.9668.1, ISNI 0000 0001 0726 2490, Institute of Clinical Medicine, Internal Medicine, , University of Eastern Finland, ; Kuopio, Finland
                [56 ]GRID grid.5326.2, ISNI 0000 0001 1940 4177, Istituto di Ricerca Genetica e Biomedica, , Consiglio Nazionale delle Ricerche (CNR), ; Monserrato, Italy
                [57 ]GRID grid.267308.8, ISNI 0000 0000 9206 2401, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, , University of Texas Health Science Center at Houston, ; Houston, TX USA
                [58 ]GRID grid.241167.7, ISNI 0000 0001 2185 3318, Department of Internal Medicine-Section on Nephrology, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [59 ]GRID grid.5947.f, ISNI 0000 0001 1516 2393, K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, , Norwegian University of Science and Technology, ; Trondheim, Norway
                [60 ]GRID grid.34477.33, ISNI 0000000122986657, Division of Pulmonary, Critical Care, and Sleep Medicine, , Department of Medicine, University of Washington, ; Seattle, WA USA
                [61 ]GRID grid.34477.33, ISNI 0000000122986657, Center for Lung Biology, Department of Medicine, , University of Washington, ; Seattle, WA USA
                [62 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, , German Research Center for Environmental Health, ; Neuherberg, Germany
                [63 ]GRID grid.2515.3, ISNI 0000 0004 0378 8438, Department of Psychiatry & Behavioral Sciences, , Boston Children’s Hospital & Harvard Medical School, ; Boston, MA USA
                [64 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Genetic Epidemiology, , QIMR Berghofer Medical Research Institute, ; Brisbane, Australia
                [65 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Division of Biostatistics, , Washington University School of Medicine, ; St. Louis, MO USA
                [66 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Epidemiology and Key Laboratory of Cardiovascular Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; Beijing, China
                [67 ]GRID grid.14013.37, ISNI 0000 0004 0640 0021, School of Engineering and Natural Sciences, , University of Iceland, ; Reykjavik, Iceland
                [68 ]GRID grid.513199.6, The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, , The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, ; Torrance, CA USA
                [69 ]GRID grid.270240.3, ISNI 0000 0001 2180 1622, Public Health Sciences Division, , Fred Hutchinson Cancer Research Center, ; Seattle, WA USA
                [70 ]GRID grid.410721.1, ISNI 0000 0004 1937 0407, Department of Medicine, , University of Mississippi Medical Center, ; Jackson, MS USA
                [71 ]GRID grid.410711.2, ISNI 0000 0001 1034 1720, Department of Sociology and the Carolina Population Center, , University of North Carolina, ; Chapel Hill, NC USA
                [72 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Epidemiology, , Tulane University, ; New Orleans, LA USA
                [73 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Translational Sciences Institute, , Tulane University, ; New Orleans, LA USA
                [74 ]GRID grid.213910.8, ISNI 0000 0001 1955 1644, McCourt School of Public Policy, , Georgetown University, ; Washington, DC USA
                [75 ]GRID grid.266190.a, ISNI 0000000096214564, Department Of Psychology and Neuroscience, , University of Colorado Boulder, ; Boulder, CO USA
                [76 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, Youth Mental Health & Technology Team, Brain and Mind Centre, , University of Sydney, ; Sydney, Australia
                [77 ]GRID grid.265892.2, ISNI 0000000106344187, Department of Epidemiology, School of Public Health, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [78 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Epidemiology, , University of Colorado Anschutz Medical Campus, ; Aurora, CO USA
                [79 ]GRID grid.241116.1, ISNI 0000000107903411, Department of Psychiatry, , University of Colorado Anschutz Medical Center, ; Denver, CO USA
                [80 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Epidemiology, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [81 ]GRID grid.38142.3c, ISNI 000000041936754X, Program in Genetic Epidemiology and Statistical Genetics, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [82 ]GRID grid.260565.2, ISNI 0000 0004 0634 0356, Institute of Preventive Medicine, , National Defense Medical Center, ; New Taipei City, Taiwan
                [83 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK
                [84 ]GRID grid.5947.f, ISNI 0000 0001 1516 2393, HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, , Norwegian University of Science and Technology (NTNU), ; Trondheim, Norway
                [85 ]GRID grid.52522.32, ISNI 0000 0004 0627 3560, Department of Research, Innovation and Education, St. Olavs Hospital, , Trondheim University Hospital, ; Trondheim, Norway
                [86 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Population Sciences Branch, National Heart, Lung, and Blood Institute, , National Institutes of Health, ; Bethesda, MD USA
                [87 ]GRID grid.278247.c, ISNI 0000 0004 0604 5314, Section of Endocrinology and Metabolism, Department of Medicine, , Taipei Veterans General Hospital, ; Taipei, Taiwan
                [88 ]GRID grid.62562.35, ISNI 0000000100301493, GenOmics, Bioinformatics, and Translational Research Center, , RTI International, ; Research Triangle Park, NC USA
                [89 ]GRID grid.62562.35, ISNI 0000000100301493, Fellow Program, RTI International, ; Research Triangle Park, NC USA
                [90 ]GRID grid.222754.4, ISNI 0000 0001 0840 2678, Institute of Data Science, , Korea University, ; Seoul, South Korea
                [91 ]GRID grid.418961.3, ISNI 0000 0004 0472 2713, Regeneron Genetics Center, ; Tarrytown, NY USA
                [92 ]GRID grid.280776.c, ISNI 0000 0004 0394 1447, Department of Population Health Sciences, , Geisinger, ; Danville, PA USA
                [93 ]GRID grid.10698.36, ISNI 0000000122483208, Department of Epidemiology, , University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                [94 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, , The University of Tokyo, ; Tokyo, Japan
                [95 ]GRID grid.251993.5, ISNI 0000000121791997, Department of Epidemiology and Population Health, , Albert Einstein College of Medicine, ; Bronx, NY USA
                [96 ]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Institute for Molecular Medicine Finland - FIMM, , University of Helsinki, ; Helsinki, Finland
                [97 ]GRID grid.266190.a, ISNI 0000000096214564, Department of Molecular, Cellular and Developmental Biology, , University of Colorado, ; Boulder, CO USA
                [98 ]GRID grid.9668.1, ISNI 0000 0001 0726 2490, Institute of Clinical Medicine, Internal Medicine, , University of Eastern Finland and Kuopio University Hospital, ; Kuopio, Finland
                [99 ]GRID grid.410705.7, ISNI 0000 0004 0628 207X, Center for Medicine and Clinical Research, , Kuopio University Hospital, ; Kuopio, Finland
                [100 ]GRID grid.62560.37, ISNI 0000 0004 0378 8294, Brigham and Women’s Hospital, Department of Medicine, , Channing Division of Network Medicine, ; Boston, MA USA
                [101 ]GRID grid.410764.0, ISNI 0000 0004 0573 0731, Department of Medical Research, , Taichung Veterans General Hospital, ; Taichung City, Taiwan
                [102 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Department of Epidemiology and Biostatistics, , School of Public Health, Peking University Health Science Center, ; Beijing, China
                [103 ]GRID grid.214458.e, ISNI 0000000086837370, Center for Statistical Genetics, Department of Biostatistics, , University of Michigan, ; Ann Arbor, MI USA
                [104 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Psychiatric Genetics, , QIMR Berghofer Medical Research Institute, ; Brisbane, Australia
                [105 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, School of Biomedical Sciences, Faculty of Medicine, , University of Queensland, ; Brisbane, Australia
                [106 ]GRID grid.1024.7, ISNI 0000000089150953, School of Biomedical Sciences, , Queensland University of Technology, ; Brisbane, Australia
                [107 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Biostatistics, , Boston University School of Public Health, ; Boston, MA USA
                [108 ]GRID grid.16753.36, ISNI 0000 0001 2299 3507, Departments of Preventive Medicine, Medicine, and Pediatrics, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
                [109 ]GRID grid.67104.34, ISNI 0000 0004 0415 0102, Department of Population Medicine, , Harvard Pilgrim Health Care Institute, ; Boston, MA USA
                [110 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Biostatics, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [111 ]GRID grid.429997.8, ISNI 0000 0004 1936 7531, Division of Nutrition Epidemiology and Data Science, Friedman School of Nutrition Science and Policy, , Tufts University, ; Boston, MA USA
                [112 ]GRID grid.27755.32, ISNI 0000 0000 9136 933X, Center for Public Health Genomics, Department of Public Health Sciences, , University of Virginia School of Medicine, ; Charlottesville, VA USA
                [113 ]GRID grid.10698.36, ISNI 0000000122483208, Department of Genetics, UNC Neuroscience Center, , University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                [114 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, , University of Maryland School of Medicine, ; Baltimore, MD USA
                [115 ]GRID grid.266190.a, ISNI 0000000096214564, Department of Integrative Physiology, , University of Colorado, ; Boulder, CO USA
                [116 ]GRID grid.280711.d, ISNI 0000 0004 0419 6661, Geriatrics Research and Education Clinical Center, , Baltimore Veterans Administration Medical Center, ; Baltimore, MD USA
                [117 ]GRID grid.410711.2, ISNI 0000 0001 1034 1720, Department of Genetics, , University of North Carolina, ; Chapel Hill, NC USA
                [118 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Internal Medicine, Division of Cardiovascular Medicine, , University of Michigan, ; Ann Arbor, MI USA
                [119 ]GRID grid.509459.4, ISNI 0000 0004 0472 0267, Laboratory for Systems Genetics, , RIKEN Center for Integrative Medical Sciences, ; Yokohama, Japan
                [120 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Department of Statistical Genetics, , Osaka University Graduate School of Medicine, ; Suita, Japan
                [121 ]GRID grid.136593.b, ISNI 0000 0004 0373 3971, Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), , Osaka University, ; Suita, Japan
                [122 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Department of Genome Informatics, Graduate School of Medicine, , the University of Tokyo, ; Tokyo, Japan
                [123 ]GRID grid.516097.c, ISNI 0000 0001 0311 6891, Population Sciences of the Pacific Program, , University of Hawaii Cancer Center, ; Honolulu, HI USA
                [124 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Epidemiology, , University of Washington, ; Seattle, WA USA
                [125 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Institute of Epidemiology, Helmholtz Zentrum München, , German Research Center for Environmental Health, ; Neuherberg, Germany
                [126 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute for Medical Information Processing, Biometry and Epidemiology, , Ludwig Maximilians University Munich, ; Munich, Germany
                [127 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, German Centre for Cardiovascular Research, , DZHK, Partner Site Munich, ; Munich, Germany
                [128 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Clinical Developmental Psychology, , Vrije Universiteit, ; Amsterdam, The Netherlands
                [129 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Department of Child and Adolescent Psychiatry, , Amsterdam UMC, ; Amsterdam, The Netherlands
                [130 ]GRID grid.239395.7, ISNI 0000 0000 9011 8547, Division of Pulmonary, Critical Care, and Sleep Medicine, , Beth Israel Deaconess Medical Center, ; Boston, MA USA
                [131 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Division of Pulmonary and Critical Care Medicine, Department of Medicine, , University of Maryland School of Medicine, ; Baltimore, MD USA
                [132 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Psychiatry, , Washington University School of Medicine, ; St. Louis, MO USA
                [133 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Center for Demography of Health and Aging, , University of Wisconsin-Madison, ; Madison, WI USA
                [134 ]GRID grid.489797.c, SAA-National Center of Addiction Medicine, , Vogur Hospital, ; Reykjavik, Iceland
                [135 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Genetics, , Washington University School of Medicine, ; St. Louis, MO USA
                [136 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Division of Pulmonary Sciences and Critical Care Medicine; Department of Medicine and Immunology, , University of Colorado, ; Aurora, CO USA
                [137 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Herbert Wertheim School of Public Health and Human Longevity Science, , University of California, San Diego, ; La Jolla, CA USA
                [138 ]GRID grid.420283.f, ISNI 0000 0004 0626 0858, 23andMe, Inc, ; Sunnyvale, CA USA
                [139 ]GRID grid.488833.c, ISNI 0000 0004 0615 7519, Kaiser Permanente Washington Health Research Institute, , Kaiser Permanente Washington, ; Seattle, WA USA
                [140 ]GRID grid.511389.7, Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, ; Seattle, WA USA
                [141 ]GRID grid.34477.33, ISNI 0000000122986657, Division of Cardiology, Department of Medicine, , University of Washington, ; Seattle, WA USA
                [142 ]GRID grid.14013.37, ISNI 0000 0004 0640 0021, Faculty of Medicine, , University of Iceland, ; Reykjavik, Iceland
                [143 ]GRID grid.477168.b, ISNI 0000 0004 5897 5206, COPD Foundation, ; Washington, DC USA
                [144 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, MRC Integrative Epidemiology Unit, Population Health Sciences, , University of Bristol, ; Bristol, UK
                [145 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, National Institute for Health Research Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol, ; Bristol, UK
                [146 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, Department of Population Health Sciences, Bristol Medical School, , University of Bristol, ; Bristol, UK
                [147 ]GRID grid.265892.2, ISNI 0000000106344187, Department of Biostatistics, School of Public Health, , University of Alabama at Birmingham, ; Birmingham, AL USA
                [148 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Psychiatry, , University of California San Diego, ; San Diego, CA USA
                [149 ]GRID grid.265109.9, ISNI 0000 0000 9002 1462, Jackson Heart Study Undergraduate Training and Education Center, Tougaloo College, ; Tougaloo, MS USA
                [150 ]GRID grid.34477.33, ISNI 0000000122986657, Department of Medicine, , University of Washington, ; Seattle, WA USA
                [151 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Internal Medicine, Division of Cardiology, , University of Michigan, ; Ann Arbor, MI USA
                [152 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Human Genetics, , University of Michigan, ; Ann Arbor, MI USA
                [153 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Computational Medicine and Bioinformatics, , University of Michigan, ; Ann Arbor, MI USA
                [154 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Department of Research and Innovation, Division of Clinical Neuroscience, , Oslo University Hospital, ; Oslo, Norway
                [155 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Department of Neurology, , Oslo University Hospital, ; Oslo, Norway
                [156 ]GRID grid.10698.36, ISNI 0000000122483208, Department of Epidemiology, Gillings School of Global Public Health, , University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                [157 ]GRID grid.32224.35, ISNI 0000 0004 0386 9924, Analytic and Translational Genetics Unit, , Massachusetts General Hospital, ; Boston, MA USA
                [158 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Biostatistics, , University of Michigan, ; Ann Arbor, MI USA
                [159 ]GRID grid.214458.e, ISNI 0000000086837370, Department of Psychiatry, , University of Michigan, ; Ann Arbor, MI USA
                [160 ]GRID grid.510779.d, ISNI 0000 0004 9414 6915, Health Data Science Centre, , Fondazione Human Technopole, ; Milan, Italy
                [161 ]GRID grid.9918.9, ISNI 0000 0004 1936 8411, Department of Population Health Sciences, , University of Leicester, ; Leicester, UK
                [162 ]GRID grid.280332.8, ISNI 0000 0001 2110 136X, Oregon Research Institute, ; Springfield, OR USA
                [163 ]GRID grid.427493.f, BioRealm, LLC, ; Walnut, CA USA
                [164 ]GRID grid.240372.0, ISNI 0000 0004 0400 4439, Outcomes Research Network & Department of Family Medicine, , NorthShore University HealthSystem, ; Evanston, IL USA
                [165 ]GRID grid.170205.1, ISNI 0000 0004 1936 7822, Department of Family Medicine, , University of Chicago, ; Chicago, IL USA
                [166 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Medicine, , Université de Montréal, ; Montréal, Québec Canada
                [167 ]GRID grid.14848.31, ISNI 0000 0001 2292 3357, Department of Neurosciences, , Université de Montréal, ; Montréal, Québec Canada
                [168 ]GRID grid.482476.b, ISNI 0000 0000 8995 9090, Research Centre, , Montréal Heart Institute, ; Montréal, Québec Canada
                [169 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, School of Psychological Science, , University of Bristol, ; Bristol, UK
                Author information
                http://orcid.org/0000-0003-3108-8204
                http://orcid.org/0000-0001-6550-6959
                http://orcid.org/0000-0002-2727-7240
                http://orcid.org/0000-0001-6553-858X
                http://orcid.org/0000-0003-3861-7930
                Article
                5477
                10.1038/s41586-022-05477-4
                9771818
                36477530
                abc531b0-4688-49db-a9c0-5f8a92b39c61
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 March 2022
                : 25 October 2022
                Categories
                Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2022

                Uncategorized
                genome-wide association studies,risk factors,human behaviour
                Uncategorized
                genome-wide association studies, risk factors, human behaviour

                Comments

                Comment on this article