July 2024

Journal

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

By:
Verma, Anurag ; Huffman, Jennifer; Rodriguez, Alexis; Liu, Molei ; Ho, Yuk-Lam; Kim, Youngdae ; Heise, David A; Panickan, Vidul; Linares, Franciel ; Costa, Lauren; Goethert, Ian D; Tipton, Ryan A; Honerlaw, Jacqueline; Davies, Laura M; Cohen, Jeremy D; Posner, Daniel; Sangar, Rahul; Murray, Michael; Wang, Xuan; Carroll, Robert; Duvall, Scott L; Gelernter, Joel E; Kember, Rachel; Kranzler, Henry; Levey, Daniel; Polimanti, Renato ; Justice, Amy; Begoli, Edmon ; Kusnezov, Dimitri; Ramoni, Rachel; Pyarajan, Saiju; Bick, Alexander; Cai, Tianxi; Cho, Kelly; Gaziano, Michael; Madduri, Ravi; Damrauer, Scott; Liao, Katherine
Journal Name:
Science
Page Number:
eadj1182
Volume:
385
Issue Number:
6706
Publication Date:
July 2024
View DOI Listing:
https://doi.org/10.1126/science.adj1182

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.