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Genome-Wide Investigation of Exogenous Female Hormones, Genetic Variation, and Venous Thromboembolism Risk

dc.rights.licenseopenen_US
dc.contributor.authorHASSER, Emily K
dc.contributor.authorBRODY, Jennifer A
dc.contributor.authorBARTZ, Traci M
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIBORD, Florian
dc.contributor.authorLI-GAO, Ruifang
dc.contributor.authorKAUKO, Anni
dc.contributor.authorWIGGINS, Kerri L
dc.contributor.authorTEDER-LAVING, Maris
dc.contributor.authorKIM, Jihye
dc.contributor.authorMUNSCH, Gaelle
dc.contributor.authorHAILE, Helen G
dc.contributor.authorDELEUZE, Jean-Francois
dc.contributor.authorVAN HYLCKAMA VLIEG, Astrid
dc.contributor.authorWOLBERG, Alisa S
dc.contributor.authorBOLAND, Anne
dc.contributor.authorMORANGE, Pierre-Emmanuel
dc.contributor.authorFINNGEN, Estonia Biobank Research Team
dc.contributor.authorKRAFT, Peter
dc.contributor.authorLOWENSTEIN, Charles J
dc.contributor.authorEMMERICH, Joseph
dc.contributor.authorSITLANI, Colleen M
dc.contributor.authorSUCHON, Pierre
dc.contributor.authorROSENDAAL, Frits R
dc.contributor.authorNIIRANEN, Teemu
dc.contributor.authorKABRHEL, Christopher
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorSMITH, Nicholas L
dc.date.accessioned2024-06-27T08:56:09Z
dc.date.available2024-06-27T08:56:09Z
dc.date.issued2024-05-21
dc.identifier.issn1538-7836en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/200669
dc.description.abstractEnBACKGROUND: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). OBJECTIVES: To investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment (GxE) case-only meta-analysis of genome-wide association studies (GWAS). METHODS: Use or non-use of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and estimated supra-multiplicative GxE interaction. The SI parameters were first meta-analyzed across OC and HT studies, and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a p-value threshold of <5.0x10(-8); secondary analyses were candidate-based. RESULTS: The VTE case-only OC meta-analysis included 2,895 OC users and 6,607 non-users; the case-only HT meta-analysis included 2,434 HT users and 12,793 non-users. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest p-value approached statistical significance: rs9386463 (p = 5.03x10(-8)). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138=3.62x10(-4)): F5 rs6025 (p = 1.87x10(-5), SI = 1.29: previously observed) and F11 rs2036914 (p = 2.0x10(-4), SI = 0.91; new observation). CONCLUSIONS: The candidate-variant approach to identify supra-multiplicative associations between genetic variation and OC-HT use identified a new association with common genetic variation in F11 while the agnostic interrogations did not yield new discoveries.
dc.language.isoENen_US
dc.subject.enEpidemiology
dc.subject.enGene-Environment Interaction
dc.subject.enHormone Replacement Therapy
dc.subject.enOral Contraceptives
dc.subject.enVenous Thromboembolism
dc.title.enGenome-Wide Investigation of Exogenous Female Hormones, Genetic Variation, and Venous Thromboembolism Risk
dc.title.alternativeJ Thromb Haemosten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.jtha.2024.05.011en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38782299en_US
bordeaux.journalJournal of Thrombosis and Haemostasisen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04626937
hal.version1
hal.date.transferred2024-06-27T08:56:14Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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