Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

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

Anurag Verma, Jennifer E. Huffman, Alex A Rodriguez, Mitchell Conery, Molei Liu, Yuk‐Lam Ho, Youngdae Kim, David Heise, Lindsay Guare, Vidul Ayakulangara Panickan, Helene Garcon, Franciel Linares, Lauren Costa, Ian Goethert, Ryan Tipton, Jacqueline Honerlaw, Laura Davies, Stacey B. Whitbourne, Jérémy Cohen, Daniel Posner, Rahul Sangar, Michael Murray, Xuan Wang, Daniel Dochtermann, Poornima Devineni, Yunling Shi, Tarak Nandi, Themistocles L. Assimes, Charles A. Brunette, Robert J. Carroll, Royce E. Clifford, Scott L. DuVall, Joel Gelernter, Adriana M. Hung, Sudha K. Iyengar, Jacob Joseph, Rachel L. Kember, Henry R. Kranzler, Colleen Morse Kripke, Daniel F. Levey, Shiuh‐Wen Luoh, Victoria C. Merritt, Cassie Overstreet, Joseph D. Deak, Struan F.A. Grant, Renato Polimanti, Panos Roussos, Gabrielle Shakt, Yan V. Sun, Noah L. Tsao, Sanan Venkatesh, Georgios Voloudakis, Amy C. Justice, Edmon Begoli, Rachel Ramoni, Georgia D. Tourassi, Saiju Pyarajan, Philip S. Tsao, Christopher J. O’Donnell, Sumitra Muralidhar, Jennifer Moser, Juan P. Casas, Alexander G. Bick, Wei Zhou, Tianxi Cai, Benjamin F. Voight, Kelly Cho, J. Michael Gaziano, Ravi Madduri, Scott M. Damrauer, Katherine P. Liao

Science · 2024

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Summary

This large-scale genome-wide association study analysed 2,068 traits in nearly 636,000 genetically diverse US Veterans, identifying over 13,600 genomic risk loci and fine-mapping causal variants at over 6,300 signals. A substantial proportion of novel genetic insights (approximately one-third of fine-mapped variants) emerged from non-European participants, demonstrating the scientific value of population diversity in genetic studies and providing an extensive atlas of trait–genetic associations.

UK applicability

The genetic architecture findings may be broadly applicable to UK populations with similar ancestry composition, though direct translation requires consideration of ethnically stratified UK cohorts. The emphasis on diverse population representation could inform future UK biobank studies and clinical genomics practice.

Key measures

Genomic risk loci count; fine-mapped causal variants; trait associations across diverse population groups; number of loci identified exclusively in non-European populations

Outcomes reported

Genome-wide associations were identified for 2,068 traits in 635,969 diverse US Veterans participants, revealing 13,672 genomic risk loci. Fine-mapping identified causal variants at 6,318 signals, with one-third discovered in non-European populations.

Theme
Measurement & metrics
Subject
Other / interdisciplinary
Study type
Research
Study design
Observational cohort
Source type
Peer-reviewed study
Status
Published
Geography
United States
System type
Human clinical
DOI
10.1126/science.adj1182
Catalogue ID
SNmoj44b9n-i0ta8i

Topic tags

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