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@ARTICLE{Mies:301998,
author = {G. Mies and N. L. Tsao and A. Houy and S. E. Coupland and
H. Kalirai and A. Försti$^*$ and K. Hemminki$^*$ and H.
Thomsen and M.-H. Stern and C. L. Shields and S. M. Damrauer
and K. G. Ewens and A. Ganguly and I. Mathieson},
title = {{M}eta-analysis of uveal melanoma genome-wide association
studies identifies novel risk loci and population effect
size heterogeneity.},
journal = {Human genetics and genomics advances},
volume = {6},
number = {3},
issn = {2666-2477},
address = {Cambridge, Ma.},
publisher = {Cell Press},
reportid = {DKFZ-2025-01197},
pages = {100465},
year = {2025},
note = {Volume 6, Issue 3, 10 July 2025, 100465},
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 5000 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 across
cohorts, in particular, a weaker association between eye
pigmentation and UM in a Finnish cohort. Finally, we confirm
differential effect sizes between uveal melanoma cases with
and without loss of chromosome 3, the major determinant of
metastatic risk. Our study identifies novel germline risk
factors for UM and highlights genetic and environmental
heterogeneity in its etiology.},
cin = {B062 / HD01 / Z999},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)Z999-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40495383},
doi = {10.1016/j.xhgg.2025.100465},
url = {https://inrepo02.dkfz.de/record/301998},
}