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Diversity and Scale: Genetic Architecture of 2,068 Traits in the VA Million Veteran Program.


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 P<4.6×10-11 significance; fine-mapping 6,318 signals identified from 613 traits to single-variant resolution. Among these, a third (2,069) of the associations were found only among participants genetically similar to non-European reference populations, demonstrating the importance of expanding diversity in genetic studies. Our work provides a comprehensive atlas of phenome-wide genetic associations for future studies dissecting the architecture of complex traits in diverse populations.

SUBMITTER: Verma A 

PROVIDER: S-EPMC10327290 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Diversity and Scale: Genetic Architecture of 2,068 Traits in the VA Million Veteran Program.

Verma Anurag A   Huffman Jennifer E JE   Rodriguez Alex A   Conery Mitchell M   Liu Molei M   Ho Yuk-Lam YL   Kim Youngdae Y   Heise David A DA   Guare Lindsay L   Panickan Vidul Ayakulangara VA   Garcon Helene H   Linares Franciel F   Costa Lauren L   Goethert Ian I   Tipton Ryan R   Honerlaw Jacqueline J   Davies Laura L   Whitbourne Stacey S   Cohen Jeremy J   Posner Daniel C DC   Sangar Rahul R   Murray Michael M   Wang Xuan X   Dochtermann Daniel R DR   Devineni Poornima P   Shi Yunling Y   Nandi Tarak Nath TN   Assimes Themistocles L TL   Brunette Charles A CA   Carroll Robert J RJ   Clifford Royce R   Duvall Scott S   Gelernter Joel J   Hung Adriana A   Iyengar Sudha K SK   Joseph Jacob J   Kember Rachel R   Kranzler Henry H   Levey Daniel D   Luoh Shiuh-Wen SW   Merritt Victoria C VC   Overstreet Cassie C   Deak Joseph D JD   Grant Struan F A SFA   Polimanti Renato R   Roussos Panos P   Sun Yan V YV   Venkatesh Sanan S   Voloudakis Georgios G   Justice Amy A   Begoli Edmon E   Ramoni Rachel R   Tourassi Georgia G   Pyarajan Saiju S   Tsao Philip S PS   O'Donnell Christopher J CJ   Muralidhar Sumitra S   Moser Jennifer J   Casas Juan P JP   Bick Alexander G AG   Zhou Wei W   Cai Tianxi T   Voight Benjamin F BF   Cho Kelly K   Gaziano Michael J MJ   Madduri Ravi K RK   Damrauer Scott M SM   Liao Katherine P KP  

medRxiv : the preprint server for health sciences 20230629


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 ge  ...[more]

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