Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction
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.; 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.; Van Den Eeden, S. K.; Chanock, S. J.; Mosley, J. D.; Conti, D. V.; Haiman, C. A.;
Show abstract
We 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 genome-wide polygenic risk scores ranged from 11.6%-16.6% in European ancestry, 5.5%-9.5% in African ancestry, 13.5%-18.2% in Hispanic/Latino, and 8.6%-15.3% in Asian ancestry, and decreased with increasing age. Mid-life genetically-adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, offering potential to personalize prostate cancer screening.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry 97%
- Role of X chromosome and dosage compensation mechanisms in complex trait genetics 94%
- A polygenic score-based approach to identify gene-drug interactions stratifying breast cancer risk 93%
Similar papers in this journal
- Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment 98%
- Rare coding variants in five DNA damage repair genes associate with timing of natural menopause 94%
- Pathway-specific polygenic scores substantially increase the discovery of gene-adiposity interactions impacting liver biomarkers 93%
Similar papers in this journal
- Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer 95%
- Role of Specialized mSWI/SNF Complexes in Prostate Cancer Lineage Plasticity 95%
- The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.