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A Mendelian randomization of gamma' and total fibrinogen levels in relation to venous thromboembolism and ischemic stroke

dc.rights.licenseopenen_US
dc.contributor.authorMANERS, J.
dc.contributor.authorGILL, D.
dc.contributor.authorPANKRATZ, N.
dc.contributor.authorLAFFAN, M. A.
dc.contributor.authorWOLBERG, A. S.
dc.contributor.authorDE MAAT, M. P. M.
dc.contributor.authorLIGTHART, S.
dc.contributor.authorTANG, W.
dc.contributor.authorWARD-CAVINESS, C. K.
dc.contributor.authorFORNAGE, M.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorDICHGANS, M.
dc.contributor.authorMCKNIGHT, B.
dc.contributor.authorBOERWINKLE, E.
dc.contributor.authorSMITH, N. L.
dc.contributor.authorMORRISON, A. C.
dc.contributor.authorDEHGHAN, A.
dc.contributor.authorDE VRIES, P. S.
dc.date.accessioned2021-03-23T09:19:38Z
dc.date.available2021-03-23T09:19:38Z
dc.date.issued2020-12-24
dc.identifier.issn0006-4971en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26786
dc.description.abstractEnFibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ') fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied two-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ' fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies. Genetic instruments for γ' fibrinogen and total fibrinogen were selected and the inverse-variance weighted MR approach was used to estimate causal effects in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger, weighted median MR, and weighted mode MR. The main inverse-variance weighted MR estimates based on a combination of 16 genetic instruments for γ' fibrinogen and 75 genetic instruments for total fibrinogen indicated a protective effect of higher γ' fibrinogen and higher total fibrinogen on VTE risk. There was also a protective effect of higher γ' fibrinogen levels on cardioembolic and large artery stroke risk. Effect estimates were consistent across sensitivity analyses. Our results provide evidence to support effects of genetically determined γ' fibrinogen on VTE and ischemic stroke risk. Further research is needed to explore mechanisms underlying these effects, and their clinical applications.
dc.language.isoENen_US
dc.title.enA Mendelian randomization of gamma' and total fibrinogen levels in relation to venous thromboembolism and ischemic stroke
dc.title.alternativeBlooden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/blood.2019004781en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33367543en_US
bordeaux.journalBlooden_US
bordeaux.page3062-3069en_US
bordeaux.volume136en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue26en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03177389
hal.version1
hal.date.transferred2021-03-23T09:19:42Z
hal.exporttrue
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