ArticlemedRxiv : the preprint server for health sciences2023
Diversity and Scale: Genetic Architecture of 2,068 Traits in the VA Million Veteran Program.
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Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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68 authors.
Anurag VermaCorporal Michael Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Jennifer E HuffmanMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Alex RodriguezData Science and Learning, Argonne National Laboratory, Lemont, IL, 60439, USA.
Mitchell ConeryDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Molei LiuDepartment of Biostatistics, Columbia University's Mailman School of Public Health, New York, NY, 10032, USA.
Yuk-Lam HoMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Youngdae KimMathematics and Computer Science Division, Argonne National Laboratory, Lemont, IL, 60439, USA.
David A HeiseNational Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Lindsay GuareDepartment of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania - Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Vidul Ayakulangara PanickanDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Helene GarconMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Franciel LinaresR&D Systems Engineering, Information Technology Services Directorate, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Lauren CostaMVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA, 02111, USA.
Ian GoethertData Management and Engineering, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Ryan TiptonKnowledge Discovery Infrastructure, Information Technology Services Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Jacqueline HonerlawMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Laura DaviesComputing and Computational Sciences Dir PMO, PMO, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Stacey WhitbourneDepartment of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Jeremy CohenNational Security Sciences Directorate, Cyber Resilience and Intelligence Division, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Daniel C PosnerMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Rahul SangarMVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA, 02111, USA.
Michael MurrayMVP Boston Coordinating Center, VA Boston Healthcare System, Boston, MA, 02111, USA.
Xuan WangDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Daniel R DochtermannVA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, 02130, USA.
Poornima DevineniVA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, 02130, USA.
Yunling ShiVA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, 02130, USA.
Tarak Nath NandiData Science and Learning, Argonne National Laboratory, Lemont, IL, 60439, USA.
Themistocles L AssimesMedicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA, 94304, USA.
Charles A BrunetteResearch Service, VA Boston Healthcare System, Boston, MA, 02130, USA.
Robert J CarrollDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, 37211, USA.
Royce CliffordResearch Department, VA San Diego Healthcare System, San Diego, CA, 92161, USA.
Scott DuvallVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, 84148, USA.
Joel GelernterPsychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.
Adriana HungMedicine, Nephrology & Hypertension, VA Tennessee Valley Healthcare System & Vanderbilt University, Nashville, TN, 37232, USA.
Sudha K IyengarPopulation and Quantitative Health Sciences, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Jacob JosephMedicine, Cardiology Section, VA Providence Healthcare System, Providence, RI, 02908, USA.
Rachel KemberMental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Henry KranzlerMental Illness Research, Education and Clinical Center, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Daniel LeveyMedicine, VA Connecticut Healthcare System West Haven, West Haven, CT, 06516, USA.
Shiuh-Wen LuohVA Portland Health Care System, Portland, OR, 97239, USA.
Victoria C MerrittResearch Department, VA San Diego Healthcare System, San Diego, CA, 92161, USA.
Cassie OverstreetPsychiatry, Human Genetics, Yale University, New Haven, CT, 06520, USA.
Joseph D DeakPsychiatry, Yale University, New Haven, CT, 06520, USA.
Struan F A GrantCenter for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Renato PolimantiPsychiatry, Yale University, New Haven, CT, 06520, USA.
Panos RoussosPsychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY, 10468, USA.
Yan V SunEpidemiology, Emory University Rollins School of Public Health, Atlanta, GA, 30322, USA.
Sanan VenkateshPsychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY, 10468, USA.
Georgios VoloudakisPsychiatry, Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center; Icahn School of Medicine at Mount Sinai, Bronx, NY, 10468, USA.
Amy JusticeMedicine, VA Connecticut Healthcare System West Haven, West Haven, CT, 06516, USA.
Edmon BegoliOak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Rachel RamoniOffice of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA.
Georgia TourassiNational Center for Computational Sciences, Oak Ridge National Laboratory, Dept of Energy, Oak Ridge, TN, 37831, USA.
Saiju PyarajanVA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, 02130, USA.
Philip S TsaoMedicine, Cardiology, VA Palo Alto Healthcare System, Palo Alto, CA, 94304, USA.
Christopher J O'DonnellMedicine, Cardiology, VA Boston Healthcare System, Boston, MA, 02130, USA.
Sumitra MuralidharOffice of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA.
Jennifer MoserOffice of Research and Development, Department of Veterans Affairs, Washington, DC, 20420, USA.
Juan P CasasMassachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
Alexander G BickDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, 37325, USA.
Wei ZhouDepartment of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Tianxi CaiDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
Benjamin F VoightCorporal Michael Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Kelly ChoDepartment of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Michael J GazianoDepartment of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
Ravi K MadduriData Science and Learning, Argonne National Laboratory, Lemont, IL, 60439, USA.
Scott M DamrauerCorporal Michael Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Katherine P LiaoMedicine, Rheumatology, VA Boston Healthcare System, Boston, MA, 02130, USA.
Funding
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8MUnderstanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9MVERITY: Value and Evidence in Rheumatology using bioInformaTics, and advanced analYticsP30AR072577 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Daniel Hal Solomon · 2017 to 2026
$9.8MFunctional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8MFrom GWAS to PheWAS: Scanning the EMR Phenome for Gene-disease AssociationsR01LM010685 · NLM · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, LISA · 2011 to 2022
$6.3MUnravelling genetic basis of comorbidity using EHR-linked biobank dataR01GM138597 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KIM, DOKYOON · 2020 to 2023
$2.2MTranslational Alcohol Research Program (TARP)T32AA028259 · NIAAA · YALE UNIVERSITY · PI COSGROVE, KELLY P., VASILIOU, VASILIS · 2020 to 2024
$1.8MCharacterizing and targeting subphenotypes of schizophrenia and bipolar disorder via individually imputed tissue and cell-type specific transcriptomesK08MH122911 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI VOLOUDAKIS, GEORGIOS · 2020 to 2023
$770kAn integrative approach to disease gene discovery combining genetic variation, gene expression, and epigenetics.R00HG012222 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI Wei Zhou · 2024 to 2026
$747kAn integrative approach to disease gene discovery combining genetic variation, gene expression, and epigenetics.K99HG012222 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI ZHOU, WEI · 2022 to 2023
$319kLarge-scale transcriptome and epigenome association analysis across multiple traitsI01BX004189 · VA · JAMES J PETERS VA MEDICAL CENTER · PI Panagiotis Roussos · 2019 to 2026
–Precision Cardio-Metabolic Phenotyping for Genetic Discovery and Risk PredictionIK2CX001780 · VA · PHILADELPHIA VA MEDICAL CENTER · PI DAMRAUER, SCOTT MICHAEL · 2018 to 2023
–BLRD VA I01 BX004189BLRD VA I01 BX004821BLRD VA I01 BX005831CSRD VA I01 CX001737CSRD VA I01 CX001849CSRD VA IK2 CX001780NHGRI NIH HHS K99 HG012222NHGRI NIH HHS R00 HG012222NIAAA NIH HHS T32 AA028259NIAMS NIH HHS P30 AR072577NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIDDK NIH HHS UM1 DK126194NIGMS NIH HHS R01 GM138597NIMH NIH HHS K08 MH122911NLM NIH HHS R01 LM010685
Abstract
Genome-wide association studies (GWAS) have underrepresented individuals from non-European populations, impeding progress in characterizing the genetic architecture and consequences of health and disease traits. To address this, we present a population-stratified phenome-wide GWAS followed by a multi-population meta-analysis for 2,068 traits derived from electronic health records of 635,969 participants in the Million Veteran Program (MVP), a longitudinal cohort study of diverse U.S. Veterans genetically similar to the respective African (121,177), Admixed American (59,048), East Asian (6,702), and European (449,042) superpopulations defined by the 1000 Genomes Project. We identified 38,270 independent variants associating with one or more traits at experiment-wide
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