Faculty, Staff and Student Publications
Language
English
Publication Date
11-20-2025
Journal
NPJ Genome Medicine
DOI
10.1038/s41525-025-00529-w
PMID
41266372
PMCID
PMC12635163
PubMedCentral® Posted Date
11-20-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We meta-analyzed >22 million variants for 398,238 women from the Ovarian Cancer Association Consortium (OCAC), UK Biobank (UKBB) and Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA) to identify novel HGSOC susceptibility loci. Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was TP53 3’-UTR SNP rs78378222-T’s association with HGSOC (per-T-allele relative risk (RR) = 1.44, 95% CI:1.28–1.62, P = 1.76 × 10−9). Polygenic scores (PGS) were developed using OCAC and CIMBA data and trained on FinnGen data. The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95% CI:1.37–1.54) per standard deviation when validated in the UKBB. This study represents the largest HGSOC GWAS to date – demonstrating that improvements in imputation reference panels and increased sample sizes help to identify HGSOC associated variants that previously went undetected, ultimately improving PGS which can improve personalized HGSOC risk prediction.
Keywords
Cancer genetics, Ovarian cancer, Cancer epidemiology, Cancer genetics, Ovarian cancer
Published Open-Access
yes
Recommended Citation
Barnes, Daniel R; Tyrer, Jonathan P; Dennis, Joe; et al., "Genome-Wide Association Study of 398,238 Women Unveils Seven Loci Associated With High-Grade Serous Ovarian Cancer" (2025). Faculty, Staff and Student Publications. 5297.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5297
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