Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Autor: Verma A; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Institute for Biomedical Informatics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Huffman JE; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.; Palo Alto Veterans Institute for Research (PAVIR), Palo Alto Health Care System, Palo Alto, CA 94304, USA.; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Rodriguez A; Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA., Conery M; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Liu M; Department of Biostatistics, Columbia University's Mailman School of Public Health, New York, NY 10032, USA., Ho YL; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA., Kim Y; Mathematics and Computer Science Division, Argonne National Laboratory, Lemont, IL 60439, USA., Heise DA; National Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Guare L; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Panickan VA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Garcon H; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA., Linares F; R&D Systems Engineering, Information Technology Services Directorate, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Costa L; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA., Goethert I; Data Management and Engineering, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Tipton R; Knowledge Discovery Infrastructure, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Honerlaw J; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA., Davies L; Computing and Computational Sciences Dir PMO, PMO, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Whitbourne S; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.; Department of Medicine, Division of Aging, Brigham and Women's Hospital, Boston, MA 02115, USA., Cohen J; National Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA., Posner DC; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA., Sangar R; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA., Murray M; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA., Wang X; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.; Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA., Dochtermann DR; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA., Devineni P; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA., Shi Y; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA., Nandi TN; Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA., Assimes TL; Medicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA., Brunette CA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; Research Service, VA Boston Healthcare System, Boston, MA 02130, USA., Carroll RJ; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37211, USA., Clifford R; Research Department, VA San Diego Healthcare System, San Diego, CA 92161, USA.; Department of Otolaryngology, UCSD San Diego, La Jolla, CA 92093, USA., Duvall S; VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA.; Internal Medicine, Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA., Gelernter J; Psychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.; VA Connecticut Healthcare System West Haven, West Haven, CT, 06516, USA., Hung A; Medicine, Nephrology & Hypertension, VA Tennessee Valley Healthcare System & Vanderbilt University, Nashville, TN 37232, USA., Iyengar SK; Departments of Population and Quantitative Health Sciences, Genetics and Genome Sciences, and Ophthalmology and Visual Sciences and the Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA., Joseph J; Medicine, Cardiology Section, VA Providence Healthcare System, Providence, RI 02908, USA.; Department of Medicine, Brown University, Providence, RI, 02908, USA., Kember R; Mental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Psychiatry, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Kranzler H; Mental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Psychiatry, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Kripke CM; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Levey D; Psychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.; Medicine, VA Connecticut Healthcare System West Haven, West Haven, CT 06516, USA., Luoh SW; VA Portland Health Care System, Portland, OR 97239, USA.; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA., Merritt VC; Research Department, VA San Diego Healthcare System, San Diego, CA 92161, USA., Overstreet C; Psychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA., Deak JD; Psychiatry, Yale University, New Haven, CT 06520, USA.; Psychiatry, VA Connecticut Healthcare System West Haven, West Haven, CT 06516, USA., Grant SFA; Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.; Department of Pediatrics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Divisions of Human Genetics and Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.; Department of Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Polimanti R; Psychiatry, Yale University, New Haven, CT 06520, USA., Roussos P; Psychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY 10468, USA., Shakt G; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Surgery, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Sun YV; Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA., Tsao N; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Surgery, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Venkatesh S; Psychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY 10468, USA., Voloudakis G; Psychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY 10468, USA., Justice A; Medicine, VA Connecticut Healthcare System West Haven, West Haven, CT 06516, USA.; Internal Medicine, General Medicine, Yale University, New Haven, CT 06520, USA.; Health Policy, Yale School of Public Health, New Haven, CT 06520, USA., Begoli E; Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA., Ramoni R; Office of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA., Tourassi G; National Center for Computational Sciences, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA., Pyarajan S; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA., Tsao P; Medicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA.; Department of Medicine, Stanford University, Palo Alto, CA, 94304, USA., O'Donnell CJ; Medicine, Cardiology, VA Boston Healthcare System, Boston, MA 02130, USA., Muralidhar S; Office of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA., Moser J; Office of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA., Casas JP; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA., Bick AG; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, 37325, USA., Zhou W; Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.; Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.; Program in Medical and Population Genetics, Cambridge, MA 02142, USA., Cai T; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Voight BF; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Department of Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Institute of Translational Medicine and Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Cho K; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.; Department of Medicine, Division of Aging, Brigham and Women's Hospital, Boston, MA 02115, USA., Gaziano JM; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.; Department of Medicine, Division of Aging, Brigham and Women's Hospital, Boston, MA 02115, USA., Madduri RK; Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA., Damrauer S; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.; Department of Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Department of Surgery, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.; Cardiovascular Institute, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA., Liao KP; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.; Medicine, Rheumatology, VA Boston Healthcare System, Boston, MA 02130, USA.; Department of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Jul 19; Vol. 385 (6706), pp. eadj1182. Date of Electronic Publication: 2024 Jul 19.
DOI: 10.1126/science.adj1182
Abstrakt: One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third ( n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.
Databáze: MEDLINE
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