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Phenome-wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers

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dc.contributor.authorMulugeta, A.
dc.contributor.authorLumsden, A.
dc.contributor.authorMadakkatel, I.
dc.contributor.authorStacey, D.
dc.contributor.authorLee, S.H.
dc.contributor.authorMäenpää, J.
dc.contributor.authorOehler, M.
dc.contributor.authorHypponen, E.
dc.date.issued2024
dc.description.abstractBackground: Ovarian cancer (OC) is commonly diagnosed among older women who have comorbidities. This hypothesis-free phenome-wide association study (PheWAS) aimed to identify comorbidities associated with OC, as well as traits that share a genetic architecture with OC. Methods: We used data from 181,203 white British female UK Biobank participants and analysed OC and OC subtype-specific genetic risk scores (OC-GRS) 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. Results: The OC-GRS was associated with 10 diseases, and the clear cell OC-GRS was associated with five diseases at the FDR threshold (p = 5.6 × 10−4). Mendelian randomizaiton analysis (MR) provided robust evidence for the association of OC with higher risk of “secondary malignant neoplasm of digestive systems” (OR 1.64, 95% CI 1.33, 2.02), “ascites” (1.48, 95% CI 1.17, 1.86), “chronic airway obstruction” (1.17, 95% CI 1.07, 1.29), and “abnormal findings on examination of the lung” (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, p ≤ 4.5 × 10−8). Colocalization analysis identified rs4449583 (from TERT locus) as the shared causal variant for OC and seborrheic keratosis. Conclusions: 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.
dc.identifier.citationCancer Medicine, 2024; 13(4, article no. e7051):1-13
dc.identifier.doi10.1002/cam4.7051
dc.identifier.issn2045-7634
dc.identifier.issn2045-7634
dc.identifier.orcidMadakkatel, I. [0000-0003-2339-5917]
dc.identifier.orcidOehler, M. [0000-0002-2651-5913]
dc.identifier.urihttps://hdl.handle.net/11541.2/38001
dc.language.isoen
dc.publisherJohn Wiley & Sons
dc.relation.fundingNHMRC 2007431 Medical Research Future Fund of Australia
dc.rightsCopyright 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1002/cam4.7051
dc.subjectcomorbidities
dc.subjectovarian cancer
dc.subjectPheWAS
dc.subjectTERT
dc.subjectUK biobank
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectComorbidity
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAged
dc.subjectFemale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.subjectBiomarkers
dc.titlePhenome-wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916840430701831

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