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

Last updated:: 7 June 2026

Author(s):: Daniel R. Barnes, Jonathan P. Tyrer, Joe Dennis, Goska Leslie, Manjeet K. Bolla, Michael Lush, Amber M. Aeilts, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Hoda Anton-Culver, Adalgeir Arason, Banu K. Arun, Judith Balmaña, Elisa V. Bandera, Rosa B. Barkardottir, Lieke P. V. Berger, Amy Berrington de Gonzalez, Pascaline Berthet, Katarzyna Białkowska, Line Bjørge, Amie M. Blanco, Marinus J. Blok, Kristie A. Bobolis, Natalia V. Bogdanova, James D. Brenton, Henriett Butz, Saundra S. Buys, Maria A. Caligo, Ian Campbell, Carmen Castillo, Kathleen B. M. Claes, Sarah V. Colonna, Linda S. Cook, Mary B. Daly, Agnieszka Dansonka-Mieszkowska, Miguel de la Hoya, Anna deFazio, Allison DePersia, Yuan Chun Ding, Jennifer A. Doherty, Susan M. Domchek, Thilo Dörk, Zakaria Einbeigi, Christoph Engel, D. Gareth Evans, Lenka Foretova, Renée T. Fortner, Florentia Fostira, Maria Cristina Foti, Eitan Friedman, Megan N. Frone, Patricia A. Ganz, Aleksandra Gentry-Maharaj, Gord Glendon, Andrew K. Godwin, Anna González-Neira, Mark H. Greene, Jacek Gronwald, Aliana Guerrieri-Gonzaga, Ute Hamann, Thomas V. O. Hansen, Holly R. Harris, Jan Hauke, Florian Heitz, Frans B. L. Hogervorst, Maartje J. Hooning, John L. Hopper, Chad D. Huff, David G. Huntsman, Evgeny N. Imyanitov, Louise Izatt, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Siddhartha Kar, Beth Y. Karlan, Catherine J. Kennedy, Lambertus A.L.M. Kiemeney, Irene Konstantopoulou, Jolanta Kupryjanczyk, Yael Laitman, Ofer Lavie, Kate Lawrenson, Jenny Lester, Fabienne Lesueur, Carlos Lopez-Pleguezuelos, Phuong L. Mai, Siranoush Manoukian, Taymaa May, Iain A. McNeish, Usha Menon, Roger L. Milne, Francesmary Modugno, Jennifer M. Mongiovi, Marco Montagna, Kirsten B. Moysich, Susan L. Neuhausen, Finn C. Nielsen, Catherine Noguès, Edit Oláh, Olufunmilayo I. Olopade, Ana Osorio, Laura Papi, Harsh Pathak, Celeste L. Pearce, Inge S. Pedersen, Ana Peixoto, Tanja Pejovic, Pei-Chen Peng, Beth N. Peshkin, Paolo Peterlongo, C. Bethan Powell, Darya Prokofyeva, Miquel Angel Pujana, Paolo Radice, Muhammad U. Rashid, Gad Rennert, George Richenberg, Dale P. Sandler, Naoko Sasamoto, Veronica W. Setiawan, Priyanka Sharma, Weiva Sieh, Christian F. Singer, Katie Snape, Anna P. Sokolenko, Penny Soucy, Melissa C. Southey, Dominique Stoppa-Lyonnet, Rebecca Sutphen, Christian Sutter, Yen Y. Tan, Manuel R. Teixeira, Kathryn L. Terry, Liv Cecilie V. Thomsen, Marc Tischkowitz, Amanda E. Toland, Toon Van Gorp, Ana Vega, Digna R. Velez Edwards, Penelope M. Webb, Jeffrey N. Weitzel, Nicolas Wentzensen, Alice S. Whittemore, Stacey J. Winham, Anna H. Wu, Siddhartha Yadav, Yao Yu, Argyrios Ziogas, Andrew Berchuck, Fergus J. Couch, Ellen L. Goode, Marc T. Goodman, Alvaro N. Monteiro, Kenneth Offit, Susan J. Ramus, Harvey A. Risch, Joellen M. Schildkraut, Mads Thomassen, Jacques Simard, Douglas F. Easton, Michelle R. Jones, Georgia Chenevix-Trench, Simon A. Gayther, Antonis C. Antoniou, Paul D. P. Pharoah
Publish date:: 20 November 2025
Journal:: npj Genomic Medicine
PubMed ID:: 41266372
DOI:: 10.1038/s41525-025-00529-w

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.