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

• 成果类型: Article
• 署名作者: Verma, Anurag; Huffman, Jennifer E.; Rodriguez, Alex; Conery, Mitchell; Liu, Molei; Ho, Yuk-Lam; Kim, Youngdae; Heise, David A.; Guare, Lindsay; Panickan, Vidul Ayakulangara; Garcon, Helene; Linares, Franciel; Costa, Lauren; Goethert, Ian; Tipton, Ryan; Honerlaw, Jacqueline; Davies, Laura; Whitbourne, Stacey; Cohen, Jeremy; Posner, Daniel C.; Sangar, Rahul; Murray, Michael; Wang, Xuan; Dochtermann, Daniel R.; Devineni, Poornima; Shi, Yunling; Nandi, Tarak Nath; Assimes, Themistocles L.; Brunette, Charles A.; Carroll, Robert J.; Clifford, Royce; Duvall, Scott; Gelernter, Joel; Hung, Adriana; Iyengar, Sudha K.; Joseph, Jacob; Kember, Rachel; Kranzler, Henry; Kripke, Colleen M.; Levey, Daniel; Luoh, Shiuh-Wen; Merritt, Victoria C.; Overstreet, Cassie; Deak, Joseph D.; Grant, Struan F. A.; Polimanti, Renato; Roussos, Panos; Shakt, Gabrielle; Sun, Yan V.; Tsao, Noah; Venkatesh, Sanan; Voloudakis, Georgios; Justice, Amy; Begoli, Edmon; Ramoni, Rachel; Tourassi, Georgia; Pyarajan, Saiju; Tsao, Philip; O'Donnell, Christopher J.; Muralidhar, Sumitra; Moser, Jennifer; Casas, Juan P.; Bick, Alexander G.; Zhou, Wei; Cai, Tianxi; Voight, Benjamin F.; Cho, Kelly; Gaziano, J. Michael; Madduri, Ravi K.; Damrauer, Scott; Liao, Katherine P.
• 署名单位: University of Pennsylvania; University of Pennsylvania; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Harvard University; Harvard Medical School; United States Department of Energy (DOE); Argonne National Laboratory; University of Pennsylvania; Columbia University; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; Harvard University; Harvard Medical School; United States Department of Energy (DOE); Oak Ridge National Laboratory; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Utah System of Higher Education; University of Utah; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; Vanderbilt University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA San Diego Healthcare System; University of California System; University of California San Diego; US Department of Veterans Affairs; Utah System of Higher Education; University of Utah; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Tennessee Valley Healthcare System; Vanderbilt University; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; Brown University; University of Pennsylvania; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Portland Health Care System; Oregon Health & Science University; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; US Department of Veterans Affairs; Veterans Health Administration (VHA); James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; Emory University; Rollins School Public Health; Yale University; Yale University; United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; Stanford University; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; Vanderbilt University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Pennsylvania; University of Pennsylvania; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9377
• DOI: 10.1126/science.adj1182
• 发表日期: 2024-07-19
• 关键词: positive selection; prostate-cancer; quality-control; biobank; disease; HEALTH; RISK; pigmentation; expression; DESIGN

摘要

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.