Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity.

ABSTRACT: Uveal melanoma (UM) is a rare but frequently metastasizing cancer. Genome-wide association studies have identified three common genome-wide significant germline risk loci. Here, we perform a genome-wide association study on 401 new cases and conduct a meta-analysis with three independent previously published cohorts for a total sample size of 2,426 cases. We confirm the three previously identified risk loci and identify four additional genome-wide significant loci. We find that eye pigmentation-decreasing variants are systematically associated with increased UM risk and that selection for lighter pigmentation in the past 5,000 years explains about 73% of the difference in UM incidence between Northern and Southern Europe. We find evidence of effect size heterogeneity at significant loci ac

SUBMITTER: Mies G 

PROVIDER: S-EPMC12226357 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature