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

Affiliations
  • 1Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
  • 2Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 3Institute for Biomedical Informatics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 4Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • 5Palo Alto Veterans Institute for Research (PAVIR), Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • 6Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • 7Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA.
  • 8Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 9Department of Biostatistics, Columbia University’s Mailman School of Public Health, New York, NY 10032, USA.
  • 10Mathematics and Computer Science Division, Argonne National Laboratory, Lemont, IL 60439, USA.
  • 11National Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • 12Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • 13R&D Systems Engineering, Information Technology Services Directorate, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • 14MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.
  • 15Data Management and Engineering, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • 16Knowledge Discovery Infrastructure, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • 17Computing and Computational Sciences Dir PMO, PMO, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • 18Department of Medicine, Division of Aging, Brigham and Women’s Hospital, Boston, MA 02115, USA.
  • 19Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA.
  • 20VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA.
  • 21Medicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA.
  • 22Research Service, VA Boston Healthcare System, Boston, MA 02130, USA.
  • 23Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37211, USA.
  • 24Research Department, VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • 25Department of Otolaryngology, UCSD San Diego, La Jolla, CA 92093, USA.
  • 26VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA.
  • 27Internal Medicine, Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
  • 28Psychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.
  • 29VA Connecticut Healthcare System West Haven, West Haven, CT, 06516, USA.
  • 30Medicine, Nephrology & Hypertension, VA Tennessee Valley Healthcare System & Vanderbilt University, Nashville, TN 37232, USA.
  • 31Departments 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.
  • 32Medicine, Cardiology Section, VA Providence Healthcare System, Providence, RI 02908, USA.
  • 33Department of Medicine, Brown University, Providence, RI, 02908, USA.
  • 34Mental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
  • 35Department of Psychiatry, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 36Medicine, VA Connecticut Healthcare System West Haven, West Haven, CT 06516, USA.
  • 37VA Portland Health Care System, Portland, OR 97239, USA.
  • 38Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
  • 39Psychiatry, Yale University, New Haven, CT 06520, USA.
  • 40Psychiatry, VA Connecticut Healthcare System West Haven, West Haven, CT 06516, USA.
  • 41Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 42Department of Pediatrics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 43Divisions of Human Genetics and Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 44Department of Genetics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 45Psychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY 10468, USA.
  • 46Department of Surgery, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 47Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA.
  • 48Internal Medicine, General Medicine, Yale University, New Haven, CT 06520, USA.
  • 49Health Policy, Yale School of Public Health, New Haven, CT 06520, USA.
  • 50Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
  • 51Office of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA.
  • 52National Center for Computational Sciences, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
  • 53Department of Medicine, Stanford University, Palo Alto, CA, 94304, USA.
  • 54Medicine, Cardiology, VA Boston Healthcare System, Boston, MA 02130, USA.
  • 55Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, 37325, USA.
  • 56Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  • 57Stanley Center for Psychiatric Research, Cambridge, MA 02142, USA.
  • 58Program in Medical and Population Genetics, Cambridge, MA 02142, USA.
  • 59Institute of Translational Medicine and Therapeutics, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 60Cardiovascular Institute, University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • 61Medicine, Rheumatology, VA Boston Healthcare System, Boston, MA 02130, USA.
  • 62Department of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Boston, MA 02115, USA.

Published on:

July 18, 2024

Abstract

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 ( = 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.

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