Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Anurag VermaJennifer E HuffmanAlex RodriguezMitchell ConeryMolei LiuYuk-Lam Anne HoYoungdae KimDavid A HeiseLindsay A GuareVidul Ayakulangara PanickanHelene GarconFranciel LinaresLauren CostaIan GoethertRyan TiptonJacqueline P HonerlawLaura DaviesStacey B WhitbourneJeremy CohenDaniel C PosnerRahul SangarMichael MurrayXuan WangDaniel R DochtermannPoornima DevineniYunling ShiTarak Nath NandiThemistocles L AssimesCharles A BrunetteRobert J CarrolRoyce E CliffordScott L DuvallJoshua C GrayAdriana M HungSudha K IyengarJacob JosephRachel L KemberHenry R KranzlerColleen M KripkeDaniel F LeveyShiuh-Wen LuohVictoria C MerrittCassie OverstreetJoseph D DeakStruan F A GrantRenato PolimantiPanagiotis RoussosGabrielle ShaktYan V SunNoah L TsaoSanan VenkateshGeorgios VoloudakisAmy JusticeEdmon BegoliRachel B RamoniGeorgia TourassiSaiju PyarajanPhilip S TsaoChristopher J O'DonnellSumitra MuralidharJennifer MoserJuan P CasasAlexander G BickWei ZhouTianxi CaiBenjamin F VoightKelly ChoJohn Michael GazianoRavi K MadduriScott M DamrauerKatherine P LiaoPublished in: Science (New York, N.Y.) (2024)
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.