Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer

DR Barnes; JP Tyrer; J Dennis; G Leslie; MK Bolla; M Lush; AM Aeilts; K Aittomäki; N Andrieu; IL Andrulis; H Anton-Culver; A Arason; BK Arun; J Balmaña; EV Bandera; RB Barkardottir; LPV Berger; A Berrington de Gonzalez; P Berthet; K Białkowska; L Bjørge; AM Blanco; MJ Blok; KA Bobolis; NV Bogdanova; JD Brenton; H Butz; SS Buys; MA Caligo; I Campbell; C Castillo; KBM Claes; SV Colonna; LS Cook; MB Daly; A Dansonka-Mieszkowska; M de la Hoya; A deFazio; A DePersia; YC Ding; JA Doherty; SM Domchek; T Dörk; Z Einbeigi; C Engel; DG Evans; L Foretova; RT Fortner; F Fostira; MC Foti; E Friedman; MN Frone; PA Ganz; A Gentry-Maharaj; G Glendon; AK Godwin; A González-Neira; MH Greene; J Gronwald; A Guerrieri-Gonzaga; U Hamann; TVO Hansen; HR Harris; J Hauke; F Heitz; FBL Hogervorst; MJ Hooning; JL Hopper; CD Huff; DG Huntsman; EN Imyanitov; L Izatt; A Jakubowska; PA James; R Janavicius; EM John; S Kar; BY Karlan; CJ Kennedy; LALM Kiemeney; I Konstantopoulou; J Kupryjanczyk; Y Laitman; O Lavie; K Lawrenson; J Lester; F Lesueur; C Lopez-Pleguezuelos; PL Mai; S Manoukian; T May; IA McNeish; U Menon; RL Milne; F Modugno; JM Mongiovi; M Montagna; KB Moysich; SL Neuhausen; FC Nielsen

Journal article

Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer

DR Barnes, JP Tyrer, J Dennis, G Leslie, MK Bolla, M Lush, AM Aeilts, K Aittomäki, N Andrieu, IL Andrulis, H Anton-Culver, A Arason, BK Arun, J Balmaña, EV Bandera, RB Barkardottir, LPV Berger, A Berrington de Gonzalez, P Berthet, K Białkowska Show all

Npj Genomic Medicine | Published : 2025

DOI: 10.1038/s41525-025-00529-w

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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 ..

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