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Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
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.
Afiliación
  • Verma A; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
  • Huffman JE; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Rodriguez A; Institute for Biomedical Informatics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Conery M; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Liu M; Palo Alto Veterans Institute for Research (PAVIR), Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Ho YL; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Kim Y; Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA.
  • Heise DA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Guare L; Department of Biostatistics, Columbia University's Mailman School of Public Health, New York, NY 10032, USA.
  • Panickan VA; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Garcon H; Mathematics and Computer Science Division, Argonne National Laboratory, Lemont, IL 60439, USA.
  • Linares F; National Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Costa L; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Goethert I; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Tipton R; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Honerlaw J; R&D Systems Engineering, Information Technology Services Directorate, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Davies L; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.
  • Whitbourne S; Data Management and Engineering, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Cohen J; Knowledge Discovery Infrastructure, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Posner DC; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Sangar R; Computing and Computational Sciences Dir PMO, PMO, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Murray M; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Wang X; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.
  • Dochtermann DR; Department of Medicine, Division of Aging, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Devineni P; National Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN 37831, USA.
  • Shi Y; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Nandi TN; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.
  • Assimes TL; MVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA 02111, USA.
  • Brunette CA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Carroll RJ; Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA.
  • Clifford R; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Duvall S; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Gelernter J; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Hung A; Data Science and Learning, Argonne National Laboratory, Lemont, IL 60439, USA.
  • Iyengar SK; Medicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA 94304, USA.
  • Joseph J; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Kember R; Research Service, VA Boston Healthcare System, Boston, MA 02130, USA.
  • Kranzler H; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37211, USA.
  • Kripke CM; Research Department, VA San Diego Healthcare System, San Diego, CA 92161, USA.
  • Levey D; Department of Otolaryngology, UCSD San Diego, La Jolla, CA 92093, USA.
  • Luoh SW; VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA.
  • Merritt VC; Internal Medicine, Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
  • Overstreet C; Psychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.
  • Deak JD; VA Connecticut Healthcare System West Haven, West Haven, CT, 06516, USA.
  • Grant SFA; Medicine, Nephrology & Hypertension, VA Tennessee Valley Healthcare System & Vanderbilt University, Nashville, TN 37232, USA.
  • Polimanti R; Departments 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.
  • Roussos P; Medicine, Cardiology Section, VA Providence Healthcare System, Providence, RI 02908, USA.
  • Shakt G; Department of Medicine, Brown University, Providence, RI, 02908, USA.
  • Sun YV; Mental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
  • Tsao N; Department of Psychiatry, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA 19104, USA.
Science ; 385(6706): eadj1182, 2024 Jul 19.
Article en En | MEDLINE | ID: mdl-39024449
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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Veteranos / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Estudio de Asociación del Genoma Completo Límite: Female / Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Veteranos / Predisposición Genética a la Enfermedad / Sitios de Carácter Cuantitativo / Estudio de Asociación del Genoma Completo Límite: Female / Humans / Male País/Región como asunto: America do norte Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos