Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups Journal Article
| Authors: | Hoffmann, T. J.; Graff, R. E.; Madduri, R. K.; Rodriguez, A. A.; Cario, C. L.; Feng, K.; Jiang, Y.; Wang, A.; Klein, R. J.; Pierce, B. L.; Eggener, S.; Tong, L.; Blot, W.; Long, J.; Goss, L. B.; Darst, B. F.; Rebbeck, T.; Lachance, J.; Andrews, C.; Adebiyi, A. O.; Adusei, B.; Aisuodionoe-Shadrach, O. I.; Fernandez, P. W.; Jalloh, M.; Janivara, R.; Chen, W. C.; Mensah, J. E.; Agalliu, I.; Berndt, S. I.; Shelley, J. P.; Schaffer, K.; Machiela, M. J.; Freedman, N. D.; Huang, W. Y.; Li, S. A.; Goodman, P. J.; Till, C.; Thompson, I.; Lilja, H.; Ranatunga, D. K.; Presti, J.; Van Den Eeden, S. K.; Chanock, S. J.; Mosley, J. D.; Conti, D. V.; Haiman, C. A.; Justice, A. C.; Kachuri, L.; Witte, J. S. |
| Article Title: | Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups |
| Abstract: | We conducted a multiancestry 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 and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (P ≤ 5 × 10−8) 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 genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino and 8.6% to 15.3% for Asian ancestry and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, offering potential to personalize prostate cancer screening. © The Author(s) 2025. |
| Keywords: | adult; controlled study; aged; major clinical study; prostate specific antigen; genome-wide association study; cancer screening; prediction; prostate cancer; veteran; hispanic; african; asian; ancestry group; human; male; article; genetic risk score; drug analysis |
| Journal Title: | Nature Genetics |
| Volume: | 57 |
| Issue: | 2 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-02-01 |
| Start Page: | 334 |
| End Page: | 344 |
| Language: | English |
| DOI: | 10.1038/s41588-024-02068-z |
| PUBMED: | 39930085 |
| PROVIDER: | scopus |
| PMCID: | PMC11821537 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
