{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:59:44Z","timestamp":1792627184227,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ovarian cancer (OC) is commonly diagnosed among older women who have comorbidities. This hypothesis\u2010free phenome\u2010wide association study (PheWAS) aimed to identify comorbidities associated with OC, as well as traits that share a genetic architecture with OC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used data from 181,203 white British female UK Biobank participants and analysed OC and OC subtype\u2010specific genetic risk scores (OC\u2010GRS) for an association with 889 diseases and 43 other traits. We conducted PheWAS and colocalization analyses for individual variants to identify evidence for shared genetic architecture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The OC\u2010GRS was associated with 10 diseases, and the clear cell OC\u2010GRS was associated with five diseases at the FDR threshold (<jats:italic>p<\/jats:italic>\u2009=\u20095.6\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Mendelian randomizaiton analysis (MR) provided robust evidence for the association of OC with higher risk of \u201csecondary malignant neoplasm of digestive systems\u201d (OR 1.64, 95% CI 1.33, 2.02), \u201cascites\u201d (1.48, 95% CI 1.17, 1.86), \u201cchronic airway obstruction\u201d (1.17, 95% CI 1.07, 1.29), and \u201cabnormal findings on examination of the lung\u201d (1.51, 95% CI 1.22, 1.87). Analyses of lung spirometry measures provided further support for compromised respiratory function. PheWAS on individual OC variants identified five genetic variants associated with other diseases, and seven variants associated with biomarkers (all, <jats:italic>p<\/jats:italic>\u2009\u2264\u20094.5\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). Colocalization analysis identified rs4449583 (from <jats:italic>TERT<\/jats:italic> locus) as the shared causal variant for OC and seborrheic keratosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>OC is associated with digestive and respiratory comorbidities. Several variants affecting OC risk were associated with other diseases and biomarkers, with this study identifying a novel genetic locus shared between OC and skin conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7051","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T15:55:55Z","timestamp":1709913355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenome\u2010wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-3454","authenticated-orcid":false,"given":"Anwar","family":"Mulugeta","sequence":"first","affiliation":[{"name":"Australian Centre for Precision Health, Unit of Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia Australia"},{"name":"Department of Pharmacology and Clinical Pharmacy, College of Health Science Addis Ababa University  Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Lumsden","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health, Unit of Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqbal","family":"Madakkatel","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health, Unit of Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stacey","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health, Unit of Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Hong","family":"Lee","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health, Unit of Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"},{"name":"South Australian Health and Medical Research Institute  Adelaide South Australia Australia"},{"name":"UniSA Allied Health &amp; Human Performance University of South Australia  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"M\u00e4enp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Medical Technology Tampere University  Tampere Finland"},{"name":"Cancer Centre, Tampere University and University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin K.","family":"Oehler","sequence":"additional","affiliation":[{"name":"Department of Gynaecological Oncology Royal Adelaide Hospital  Adelaide South Australia 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