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

Anurag Verma; Jennifer E. Huffman; Alex A Rodriguez; Mitchell Conery; Molei Liu; Yuk‐Lam Ho; Youngdae Kim; David Heise; Lindsay Guare; Vidul Ayakulangara Panickan; Helene Garcon; Franciel Linares; Lauren Costa; Ian Goethert; Ryan Tipton; Jacqueline Honerlaw; Laura Davies; Stacey B. Whitbourne; Jérémy Cohen; Daniel Posner; Rahul Sangar; Michael Murray; Xuan Wang; Daniel Dochtermann; Poornima Devineni; Yunling Shi; Tarak Nandi; Themistocles L. Assimes; Charles A. Brunette; Robert J. Carroll; Royce E. Clifford; Scott L. DuVall; Joel Gelernter; Adriana M. Hung; Sudha K. Iyengar; Jacob Joseph; Rachel L. Kember; Henry R. Kranzler; Colleen Morse Kripke; Daniel F. Levey; Shiuh‐Wen Luoh; Victoria C. Merritt; Cassie Overstreet; Joseph D. Deak; Struan F.A. Grant; Renato Polimanti; Panos Roussos; Gabrielle Shakt; Yan V. Sun; Noah L. Tsao; Sanan Venkatesh; Georgios Voloudakis; Amy C. Justice; Edmon Begoli; Rachel Ramoni; Georgia D. Tourassi; Saiju Pyarajan; Philip S. Tsao; Christopher J. O’Donnell; Sumitra Muralidhar; Jennifer Moser; Juan P. Casas; Alexander G. Bick; Wei Zhou; Tianxi Cai; Benjamin F. Voight; Kelly Cho; J. Michael Gaziano; Ravi Madduri; Scott M. Damrauer; Katherine P. Liao

doi:10.1126/science.adj1182

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

Anurag Verma(Translational Therapeutics (United States)), Jennifer E. Huffman(Harvard University), Alex A Rodriguez(Argonne National Laboratory), Mitchell Conery(Translational Therapeutics (United States)), Molei Liu(New York University), Yuk‐Lam Ho(VA Boston Healthcare System), Youngdae Kim(Argonne National Laboratory), David Heise(Oak Ridge National Laboratory), Lindsay Guare(Translational Therapeutics (United States)), Vidul Ayakulangara Panickan(Harvard University), Helene Garcon(VA Boston Healthcare System), Franciel Linares(Oak Ridge National Laboratory), Lauren Costa(VA Boston Healthcare System), Ian Goethert(Oak Ridge National Laboratory), Ryan Tipton(Oak Ridge National Laboratory), Jacqueline Honerlaw(VA Boston Healthcare System), Laura Davies(Oak Ridge National Laboratory), Stacey B. Whitbourne(Brigham and Women's Hospital), Jérémy Cohen(Oak Ridge National Laboratory), Daniel Posner(VA Boston Healthcare System), Rahul Sangar(VA Boston Healthcare System), Michael Murray(VA Boston Healthcare System), Xuan Wang(Harvard University), Daniel Dochtermann(VA Boston Healthcare System), Poornima Devineni(VA Boston Healthcare System), Yunling Shi(VA Boston Healthcare System), Tarak Nandi(Argonne National Laboratory), Themistocles L. Assimes(VA Palo Alto Health Care System), Charles A. Brunette(Harvard University), Robert J. Carroll(Vanderbilt University Medical Center), Royce E. Clifford(University of California San Diego), Scott L. DuVall(University of Utah), Joel Gelernter(Yale University), Adriana M. Hung(VA Tennessee Valley Healthcare System), Sudha K. Iyengar(Case Western Reserve University), Jacob Joseph(Brown University), Rachel L. Kember(Philadelphia VA Medical Center), Henry R. Kranzler(Philadelphia VA Medical Center), Colleen Morse Kripke(Translational Therapeutics (United States)), Daniel F. Levey(Yale University), Shiuh‐Wen Luoh(Oregon Health & Science University), Victoria C. Merritt(VA San Diego Healthcare System), Cassie Overstreet(Yale University), Joseph D. Deak(Yale University), Struan F.A. Grant(Children's Hospital of Philadelphia), Renato Polimanti(Yale University), Panos Roussos(James J. Peters VA Medical Center), Gabrielle Shakt(Philadelphia VA Medical Center), Yan V. Sun(Emory University), Noah L. Tsao(Philadelphia VA Medical Center), Sanan Venkatesh(James J. Peters VA Medical Center), Georgios Voloudakis(James J. Peters VA Medical Center), Amy C. Justice(Yale University), Edmon Begoli(Oak Ridge National Laboratory), Rachel Ramoni(VA Office of Research and Development), Georgia D. Tourassi(Oak Ridge National Laboratory), Saiju Pyarajan(VA Boston Healthcare System), Philip S. Tsao(VA Palo Alto Health Care System), Christopher J. O’Donnell(VA Boston Healthcare System), Sumitra Muralidhar(VA Office of Research and Development), Jennifer Moser(VA Office of Research and Development), Juan P. Casas(VA Boston Healthcare System), Alexander G. Bick(Vanderbilt University), Wei Zhou(Broad Institute), Tianxi Cai(Harvard University), Benjamin F. Voight(Translational Therapeutics (United States)), Kelly Cho(Brigham and Women's Hospital), J. Michael Gaziano(Brigham and Women's Hospital), Ravi Madduri(Argonne National Laboratory), Scott M. Damrauer(Philadelphia VA Medical Center), Katherine P. Liao(Brigham and Women's Hospital)

Science

July 18, 2024

10.1126/science.adj1182

Cited by 349Open Access

Full Text

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 ( 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.

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