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

Journal Article · · Science
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  1. Corporal Michael Crescenz VA Medical Center, Philadelphia, PA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
  2. VA Boston Healthcare System, MA (United States). Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC); Palo Alto Health Care System, CA (United States). Palo Alto Veterans Institute for Research (PAVIR); Harvard Medical School, Boston, MA (United States)
  3. Argonne National Laboratory (ANL), Argonne, IL (United States)
  4. Univ. of Pennsylvania, Philadelphia, PA (United States)
  5. Columbia Univ., New York, NY (United States)
  6. VA Boston Healthcare System, MA (United States). Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC)
  7. Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
  8. Harvard Medical School, Boston, MA (United States)
  9. VA Boston Healthcare System, Boston, MA (United States). MVP Boston Coordinating Center
  10. Harvard Medical School, Boston, MA (United States); VA Boston Healthcare System, Boston, MA (United States). MVP Boston Coordinating Center; Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
  11. Harvard Medical School, Boston, MA (United States); Univ. of Utah, Salt Lake City, UT (United States)
  12. VA Boston Healthcare System, Boston, MA (United States)
  13. VA Palo Alto Healthcare System, CA (United States)
  14. Harvard Medical School, Boston, MA (United States); VA Boston Healthcare System, Boston, MA (United States)
  15. Vanderbilt Univ., Nashville, TN (United States)
  16. VA San Diego Healthcare System, CA (United States); Univ. of California, San Diego, CA (United States)
  17. VA Salt Lake City Health Care System, UT (United States); Univ. of Utah, Salt Lake City, UT (United States)
  18. VA Connecticut Healthcare System West Haven, CT (United States); Yale Univ., New Haven, CT (United States)
  19. Vanderbilt Univ., Nashville, TN (United States). VA Tennessee Valley Healthcare System
  20. Case Western Reserve Univ., Cleveland, OH (United States)
  21. VA Providence Healthcare System, RI (United States); Brown Univ., Providence, RI (United States)
  22. VA Portland Health Care System, OR (United States); Oregon Health & Science Univ., Portland, OR (United States)
  23. VA San Diego Healthcare System, CA (United States)
  24. Yale Univ., New Haven, CT (United States)
  25. Icahn School of Medicine at Mount Sinai, Bronx, NY (United States). James J. Peters VA Medical Center
  26. Emory Univ., Atlanta, GA (United States)
  27. Department of Veterans Affairs, Washington, DC (United States)
  28. Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). National Center for Computational Sciences (NCCS)
  29. VA Palo Alto Healthcare System, CA (United States); Stanford Univ., CA (United States)
  30. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
  31. VA Boston Healthcare System, MA (United States). Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC); Harvard Medical School, Boston, MA (United States); Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
+ Show Author Affiliations
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.
Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
Department of Veterans Affairs; National Institutes of Health (NIH); USDOE Office of Science (SC)
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
2406806
Journal Information:
Science, Journal Name: Science Journal Issue: 6706 Vol. 385; ISSN 0036-8075
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

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