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Effects of thyroid function on hemostasis, coagulation, and fibrinolysis: a Mendelian Randomization study

dc.rights.licenseopenen_US
dc.contributor.authorELLERVIK, Christina
dc.contributor.authorMORA, Samia
dc.contributor.authorKUS, Aleksander
dc.contributor.authorASVOLD, Bjorn Olav
dc.contributor.authorMAROULI, Eirini
dc.contributor.authorDELOUKAS, Panos
dc.contributor.authorSTERENBORG, Rosalie B. T. M.
dc.contributor.authorTEUMER, Alexandre
dc.contributor.authorBURGESS, Stephen
dc.contributor.authorSABATER-LLEAL, Maria
dc.contributor.authorHUFFMAN, Jennifer
dc.contributor.authorJOHNSON, Andrew D.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorSMITH, Nicolas L.
dc.contributor.authorMEDICI, Marco
dc.contributor.authorDEVRIES, Paul S.
dc.contributor.authorCHASMAN, Daniel I.
dc.contributor.authorKJAERGAARD, Alisa D.
dc.date.accessioned2021-08-27T14:40:27Z
dc.date.available2021-08-27T14:40:27Z
dc.date.issued2021-07-01
dc.identifier.issn1050-7256en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/110236
dc.description.abstractEnBACKGROUND: Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on hemostasis, coagulation, and fibrinolysis are unknown. METHODS: In a two sample Mendelian Randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism (N=134,641), normal-range TSH (N=54,288) and fT4 (N=49,269), hyperthyroidism (N=51,823), and thyroid peroxidase antibody positivity (TPOAb) (N=25,821) on coagulation (APTT, VWF, factor VIII, PT, factor VII, fibrinogen) and fibrinolysis (D-dimer, TPA, PAI1) from the CHARGE Hemostasis Consortium (N=2,583-120,246). Inverse-variance-weighted random effects was the main MR analysis followed by sensitivity analyses. Two-sided p<0.05 was nominally significant and p<0.0011[=0.05/(5 exposures x 9 outcomes)] was Bonferroni significant for the main MR analysis. RESULTS: Genetically increased TSH was associated with decreased VWF [beta(SE)=-0.020(0.006), p=0.001] and with decreased fibrinogen [beta(SE)=-0.008(0.002), p=0.001]. Genetically increased fT4 was associated with increased VWF [beta(SE)=0.028(0.011), p=0.012]. Genetically predicted hyperthyroidism was associated with increased VWF [beta(SE)=0.012(0.004), p=0.006] and increased FVIII [beta(SE)=0.013(0.005), p=0.007]. Genetically predicted hypothyroidism and hyperthyroidism were associated with decreased TPA [beta(SE)=-0.009(0.024), p=0.024] and increased TPA [beta(SE)=0.022(0.008), p=0.008], respectively. MR sensitivity analyses showed similar direction but lower precision. Other coagulation and fibrinolytic factors were inconclusive. CONCLUSIONS: In the largest genetic studies currently available, genetically increased TSH and fT4 may be associated with decreased and increased synthesis of VWF, respectively. Since Bonferroni correction may be too conservative given the correlation between the analyzed traits, we cannot reject nominal associations of thyroid traits with coagulation or fibrinolytic factors.
dc.language.isoENen_US
dc.subject.enCoagulation
dc.subject.enFibrinolysis
dc.subject.enHemostasis
dc.subject.enHyperthyroidism
dc.subject.enHypothyroidism
dc.subject.enThyroid hormone
dc.subject.enThyroid peroxidase antibody
dc.subject.enThyrotropin
dc.title.enEffects of thyroid function on hemostasis, coagulation, and fibrinolysis: a Mendelian Randomization study
dc.typeArticle de revueen_US
dc.identifier.doi10.1089/thy.2021.0055en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed34210154en_US
dc.description.sponsorshipEuropeProgram Initiative d’Excellenceen_US
bordeaux.journalThyroiden_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDUniversité de Bordeauxen_US
hal.identifierhal-03327938
hal.version1
hal.date.transferred2021-08-27T14:40:31Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Thyroid&amp;rft.date=2021-07-01&amp;rft.eissn=1050-7256&amp;rft.issn=1050-7256&amp;rft.au=ELLERVIK,%20Christina&amp;MORA,%20Samia&amp;KUS,%20Aleksander&amp;ASVOLD,%20Bjorn%20Olav&amp;MAROULI,%20Eirini&amp;rft.genre=article


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