{"doi":"10.1101/2024.02.29.24303243","title":"Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk","abstract":"ABSTRACT Background Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1 / BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan Results Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3’-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10 -9 ). 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 in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.","journal":"medRxiv","year":2024,"id":486780,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":21839,"name":"Jonathan P. Tyrer","orcid":"0000-0003-3724-4757","position":1,"is_corresponding":false},{"id":55319,"name":"Joe Dennis","orcid":"0000-0003-4591-1214","position":2,"is_corresponding":false},{"id":254452,"name":"Goska Leslie","orcid":"0000-0001-5756-6222","position":3,"is_corresponding":false},{"id":55306,"name":"Manjeet K. Bolla","orcid":"0000-0002-4351-9326","position":4,"is_corresponding":false},{"id":249318,"name":"Michael Lush","orcid":"0000-0001-5945-3440","position":5,"is_corresponding":false},{"id":967824,"name":"Amber M. Aeilts","orcid":"0000-0001-8907-7853","position":6,"is_corresponding":false},{"id":1011451,"name":"Kristiina Aittomäki","orcid":"0000-0002-2474-1378","position":7,"is_corresponding":false},{"id":724264,"name":"Nadine Andrieu","orcid":"0000-0001-8820-5550","position":8,"is_corresponding":false},{"id":55303,"name":"Irene L. Andrulis","orcid":"0000-0002-4226-6435","position":9,"is_corresponding":false},{"id":225488,"name":"Hoda Anton‐Culver","orcid":"0000-0002-9603-0110","position":10,"is_corresponding":false},{"id":249322,"name":"Aðalgeir Arason","orcid":"0000-0003-0480-886X","position":11,"is_corresponding":false},{"id":225491,"name":"Banu Arun","orcid":"0000-0002-5475-8509","position":12,"is_corresponding":false},{"id":249324,"name":"Judith Balmañà","orcid":"0000-0002-0762-6415","position":13,"is_corresponding":false},{"id":71791,"name":"Elisa V. Bandera","orcid":"0000-0002-8789-2755","position":14,"is_corresponding":false},{"id":249325,"name":"Rósa B. Barkardóttir","orcid":"0000-0003-0629-2772","position":15,"is_corresponding":false},{"id":915702,"name":"Lieke P. V. Berger","orcid":"0000-0003-3185-559X","position":16,"is_corresponding":false},{"id":251248,"name":"Amy Berrington de González","orcid":"0000-0002-7332-8387","position":17,"is_corresponding":false},{"id":610472,"name":"Pascaline Berthet","orcid":null,"position":18,"is_corresponding":false},{"id":225496,"name":"Katarzyna Białkowska","orcid":"0000-0001-8489-6665","position":19,"is_corresponding":false},{"id":559343,"name":"Line Bjørge","orcid":"0000-0002-0240-2770","position":20,"is_corresponding":false},{"id":249326,"name":"Amie Blanco","orcid":"0000-0003-3690-0038","position":21,"is_corresponding":false},{"id":374544,"name":"Marinus J. Blok","orcid":"0000-0002-7935-5933","position":22,"is_corresponding":false},{"id":1330909,"name":"Kristie Bobolis","orcid":null,"position":23,"is_corresponding":false},{"id":225499,"name":"Natalia Bogdanova","orcid":"0000-0002-9736-4593","position":24,"is_corresponding":false},{"id":23326,"name":"James D. Brenton","orcid":"0000-0002-5738-6683","position":25,"is_corresponding":false},{"id":1330550,"name":"Henriett Butz","orcid":"0000-0003-1664-409X","position":26,"is_corresponding":false},{"id":225504,"name":"Saundra S. Buys","orcid":"0000-0003-4120-5697","position":27,"is_corresponding":false},{"id":225506,"name":"Maria A. Caligo","orcid":"0000-0003-0589-1829","position":28,"is_corresponding":false},{"id":249328,"name":"Ian Campbell","orcid":"0000-0002-7773-4155","position":29,"is_corresponding":false},{"id":897230,"name":"Carmen J. Contreras‐Castillo","orcid":"0000-0002-0554-4694","position":30,"is_corresponding":false},{"id":225510,"name":"Kathleen Claes","orcid":"0000-0003-0841-7372","position":31,"is_corresponding":false},{"id":252625,"name":"GEMO Study Collaborators","orcid":null,"position":32,"is_corresponding":false},{"id":252626,"name":"EMBRACE Collaborators","orcid":null,"position":33,"is_corresponding":false},{"id":312447,"name":"Sarah V. Colonna","orcid":"0000-0002-9026-6990","position":34,"is_corresponding":false},{"id":305535,"name":"Linda S. Cook","orcid":"0000-0001-8641-0710","position":35,"is_corresponding":false},{"id":309116,"name":"Mary B. Daly","orcid":"0000-0002-7490-6038","position":36,"is_corresponding":false},{"id":1330551,"name":"Agnieszka Dansonka‐Mieszkowska","orcid":"0000-0002-2482-6523","position":37,"is_corresponding":false},{"id":249332,"name":"Miguel de la Hoya","orcid":"0000-0002-8113-1410","position":38,"is_corresponding":false},{"id":14293,"name":"Anna deFazio","orcid":"0000-0003-0057-4744","position":39,"is_corresponding":false},{"id":855119,"name":"Allison DePersia","orcid":"0000-0001-8338-3112","position":40,"is_corresponding":false},{"id":249333,"name":"Yuan Chun Ding","orcid":"0000-0001-5578-6942","position":41,"is_corresponding":false},{"id":78635,"name":"Susan M. Domchek","orcid":"0000-0002-5914-7272","position":42,"is_corresponding":false},{"id":225515,"name":"Thilo Dörk","orcid":"0000-0002-9458-0282","position":43,"is_corresponding":false},{"id":1330552,"name":"Zakaria Einbeigi","orcid":"0000-0003-2507-7197","position":44,"is_corresponding":false},{"id":249338,"name":"Christoph Engel","orcid":"0000-0002-7247-282X","position":45,"is_corresponding":false},{"id":52732,"name":"D. Gareth Evans","orcid":"0000-0002-8482-5784","position":46,"is_corresponding":false},{"id":225519,"name":"Lenka Foretová","orcid":"0000-0003-0494-2620","position":47,"is_corresponding":false},{"id":33534,"name":"Renée T. Fortner","orcid":"0000-0002-1426-8505","position":48,"is_corresponding":false},{"id":225520,"name":"Florentia Fostira","orcid":"0000-0003-2751-2332","position":49,"is_corresponding":false},{"id":1313310,"name":"Maria Cristina Foti","orcid":"0000-0002-0694-7241","position":50,"is_corresponding":false},{"id":225521,"name":"Eitan Friedman","orcid":"0000-0002-6745-1733","position":51,"is_corresponding":false},{"id":54392,"name":"Megan N. Frone","orcid":"0000-0001-8273-8866","position":52,"is_corresponding":false},{"id":7910,"name":"Patricia A. Ganz","orcid":"0000-0002-1841-4143","position":53,"is_corresponding":false},{"id":50143,"name":"Aleksandra Gentry-Maharaj","orcid":"0000-0001-7270-9762","position":54,"is_corresponding":false},{"id":312453,"name":"Gord Glendon","orcid":"0000-0001-8630-6673","position":55,"is_corresponding":false},{"id":34241,"name":"Andrew K. Godwin","orcid":"0000-0002-3987-9580","position":56,"is_corresponding":false},{"id":84153,"name":"Anna González‐Neira","orcid":"0000-0002-5421-2020","position":57,"is_corresponding":false},{"id":78619,"name":"Mark H. Greene","orcid":"0000-0003-1852-9239","position":58,"is_corresponding":false},{"id":50159,"name":"Jacek Gronwald","orcid":"0000-0002-3643-2871","position":59,"is_corresponding":false},{"id":784869,"name":"Aliana Guerrieri‐Gonzaga","orcid":"0000-0003-1915-1688","position":60,"is_corresponding":false},{"id":55329,"name":"Ute Hamann","orcid":"0000-0002-5294-6266","position":61,"is_corresponding":false},{"id":254466,"name":"Thomas van Overeem Hansen","orcid":"0000-0003-4635-2653","position":62,"is_corresponding":false},{"id":33532,"name":"Holly R. Harris","orcid":"0000-0002-2572-6727","position":63,"is_corresponding":false},{"id":868752,"name":"Jan Hauke","orcid":"0000-0001-8236-4075","position":64,"is_corresponding":false},{"id":559349,"name":"Florian Heitz","orcid":"0000-0002-2412-0352","position":65,"is_corresponding":false},{"id":313274,"name":"Frans B.L. Hogervorst","orcid":null,"position":66,"is_corresponding":false},{"id":55331,"name":"Maartje J. Hooning","orcid":"0000-0001-6763-0857","position":67,"is_corresponding":false},{"id":228672,"name":"John L. Hopper","orcid":"0000-0002-8567-173X","position":68,"is_corresponding":false},{"id":4466,"name":"Chad D. Huff","orcid":"0000-0002-1100-9364","position":69,"is_corresponding":false},{"id":1715,"name":"David G. Huntsman","orcid":"0000-0003-4934-3322","position":70,"is_corresponding":false},{"id":543861,"name":"Evgeny N. Imyanitov","orcid":"0000-0003-4529-7891","position":71,"is_corresponding":false},{"id":252627,"name":"KConFab Investigators","orcid":null,"position":72,"is_corresponding":false},{"id":638518,"name":"Louise Izatt","orcid":"0000-0003-1258-4843","position":73,"is_corresponding":false},{"id":353561,"name":"Anna Jakubowska","orcid":"0000-0002-5650-0501","position":74,"is_corresponding":false},{"id":254676,"name":"Paul A. James","orcid":"0000-0002-4361-4657","position":75,"is_corresponding":false},{"id":254473,"name":"Ramūnas Janavičius","orcid":"0000-0002-3773-8485","position":76,"is_corresponding":false},{"id":6558,"name":"Esther M. John","orcid":"0000-0003-3259-8003","position":77,"is_corresponding":false},{"id":249315,"name":"Siddhartha Kar","orcid":"0000-0002-2314-1426","position":78,"is_corresponding":false},{"id":1719,"name":"Beth Y. Karlan","orcid":"0000-0002-9451-2933","position":79,"is_corresponding":false},{"id":13652,"name":"Catherine J. Kennedy","orcid":"0000-0002-4465-5784","position":80,"is_corresponding":false},{"id":21903,"name":"Lambertus A. Kiemeney","orcid":"0000-0002-2368-1326","position":81,"is_corresponding":false},{"id":312457,"name":"Irene Konstantopoulou","orcid":"0000-0002-0470-0309","position":82,"is_corresponding":false},{"id":491729,"name":"Jolanta Kupryjańczyk","orcid":"0000-0001-5820-0214","position":83,"is_corresponding":false},{"id":401362,"name":"Yael Laitman","orcid":null,"position":84,"is_corresponding":false},{"id":1283425,"name":"Ofer Lavie","orcid":"0000-0003-0809-3777","position":85,"is_corresponding":false},{"id":321180,"name":"Kate Lawrenson","orcid":"0000-0002-6469-2515","position":86,"is_corresponding":false},{"id":33537,"name":"Jenny Lester","orcid":"0000-0003-4914-3275","position":87,"is_corresponding":false},{"id":312458,"name":"Fabienne Lesueur","orcid":"0000-0001-7404-4549","position":88,"is_corresponding":false},{"id":1330553,"name":"Carlos Lopez-Pleguezuelos","orcid":"0009-0000-8898-5710","position":89,"is_corresponding":false},{"id":256952,"name":"Phuong L. Mai","orcid":null,"position":90,"is_corresponding":false},{"id":240378,"name":"Siranoush Manoukian","orcid":"0000-0002-6034-7562","position":91,"is_corresponding":false},{"id":559996,"name":"Taymaa May","orcid":null,"position":92,"is_corresponding":false},{"id":33525,"name":"Iain A. McNeish","orcid":"0000-0002-9387-7586","position":93,"is_corresponding":false},{"id":33584,"name":"Usha Menon","orcid":"0000-0003-3708-1732","position":94,"is_corresponding":false},{"id":34653,"name":"Roger L. Milne","orcid":"0000-0001-5764-7268","position":95,"is_corresponding":false},{"id":247744,"name":"Francesmary Modugno","orcid":"0000-0003-0637-1534","position":96,"is_corresponding":false},{"id":723419,"name":"Jennifer M. Mongiovi","orcid":"0000-0002-2083-8359","position":97,"is_corresponding":false},{"id":312461,"name":"Marco Montagna","orcid":"0000-0002-4929-2150","position":98,"is_corresponding":false},{"id":264808,"name":"Kirsten B. Moysich","orcid":"0000-0002-4678-2058","position":99,"is_corresponding":false},{"id":225484,"name":"Daniel R. Barnes","orcid":"0000-0002-3781-7570","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38496424","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}