Author:
Hoffmann Thomas J,Graff Rebecca E,Madduri Ravi K,Rodriguez Alex A,Cario Clint L,Feng Karen,Jiang Yu,Wang Anqi,Klein Robert J,Pierce Brandon L,Eggener Scott,Tong Lin,Blot William,Long Jirong,Rebbeck Timothy,Lachance Joseph,Andrews Caroline,Adebiyi Akindele O,Adusei Ben,Aisuodionoe-Shadrach Oseremen I,Fernandez Pedro W,Jalloh Mohamed,Janivara Rohini,Chen Wenlong C,Mensah James E,Agalliu Ilir,Berndt Sonja I,Shelley John P,Schaffer Kerry,Machiela Mitchell J,Freedman Neal D,Huang Wen-Yi,Li Shengchao A,Goodman Phyllis J,Till Cathee,Thompson Ian,Lilja Hans,Van Den Eeden Stephen K,Chanock Stephen J,Mosley Jonathan D,Conti David V,Haiman Christopher A,Justice Amy C,Kachuri Linda,Witte John S
Abstract
AbstractWe conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
Publisher
Cold Spring Harbor Laboratory