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dc.contributor.authorAllarai, Elias
dc.contributor.authorLee, Wei-Hsuan
dc.contributor.authorBurgess, Stephen
dc.contributor.authorLarsson, Susanna C.
dc.contributor.authorLindstrom, Sara
dc.contributor.authorWang, Lu
dc.contributor.authorSmith, Erin N.
dc.contributor.authorGordon, William
dc.contributor.authorVan Hylckama Vlieg, Astrid
dc.contributor.authorDe Andrade, Mariza
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorPattee, Jack W.
dc.contributor.authorHaessler, Jeffrey
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorSuchon, Pierre
dc.contributor.authorChen, Ming-Huei
dc.contributor.authorTurman, Constance
dc.contributor.authorGermain, Marine
dc.contributor.authorWiggins, Kerri L.
dc.contributor.authorMacdonald, James
dc.contributor.authorBrækkan, Sigrid Kufaas
dc.contributor.authorArmasu, Sebastian M.
dc.contributor.authorPankratz, Nathan
dc.contributor.authorJackson, Rabecca D.
dc.contributor.authorNielsen, Jonas B
dc.contributor.authorGiulianini, Franco
dc.contributor.authorPuurunen, Marja K.
dc.contributor.authorIbrahim, Manal
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorBammler, Theo K.
dc.contributor.authorFrazer, Kelly A.
dc.contributor.authorMccauley, Bryan M.
dc.contributor.authorTaylor, Kent
dc.contributor.authorPankow, James S.
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorGabrielsen, Maiken Elvestad
dc.contributor.authorDeleuze, Jean-Francois
dc.contributor.authorO'Donnell, Chris J.
dc.contributor.authorKim, Jihye
dc.contributor.authorMcknight, Barbara
dc.contributor.authorKraft, Peter
dc.contributor.authorHansen, John Bjarne
dc.contributor.authorRosendaal, Frits Richard
dc.contributor.authorHeit, John A.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorTang, Weihong
dc.contributor.authorKooperberg, Charles
dc.contributor.authorHveem, Kristian
dc.contributor.authorRidker, Paul M.
dc.contributor.authorMorange, Pierre-Emmanuel
dc.contributor.authorJohnson, Andrew D.
dc.contributor.authorKabrhel, Christopher
dc.contributor.authorAlexandretrégouët, David
dc.contributor.authorSmith, Nicholas L.
dc.date.accessioned2022-12-20T08:49:53Z
dc.date.available2022-12-20T08:49:53Z
dc.date.issued2022-08-19
dc.description.abstractIntroduction - In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization.<p> <p>Methods - Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed.<p> <p>Results - Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p<0.001). The association was stronger for deep vein thrombosis (OR 0.69, 95% CI 0.55–0.88, p = 0.003) than for pulmonary embolism which did not achieve statistical significance (OR 0.83, 95% CI 0.63–1.09, p = 0.184). Adjusting for genetically predicted systolic blood pressure inverted the direction of the point estimate for VTE, although the resulting CI was wide (OR 1.06, 95% CI 0.70–1.61, p = 0.780).<p> <p>Conclusions - This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for.en_US
dc.identifier.citationAllarai, Lee, Burgess, Larsson, Lindstrom, Wang, Smith, Gordon, Van Hylckama Vlieg, De Andrade, Brody, Pattee, Haessler, Brumpton, Chasman, Suchon, Chen, Turman, Germain, Wiggins, Macdonald, Brækkan, Armasu, Pankratz, Jackson, Nielsen, Giulianini, Puurunen, Ibrahim, Heckbert, Bammler, Frazer, Mccauley, Taylor, Pankow, Reiner, Gabrielsen, Deleuze, O'Donnell, Kim, Mcknight, Kraft, Hansen, Rosendaal, Heit, Psaty, Tang, Kooperberg, Hveem, Ridker, Morange, Johnson, Kabrhel, Alexandretrégouët, Smith. Genetically predicted cortisol levels and risk of venous thromboembolism. PLOS ONE. 2022;17(8)en_US
dc.identifier.cristinIDFRIDAID 2071649
dc.identifier.doi10.1371/journal.pone.0272807
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/27885
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLOS ONE
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleGenetically predicted cortisol levels and risk of venous thromboembolismen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)