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Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes A Mendelian Randomization Study

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dc.contributor.authorLarsson, Susanna C
dc.contributor.authorTraylor, Matthew
dc.contributor.authorMishra, Aniket
dc.contributor.authorHowson, Joanna MM
dc.contributor.authorMichaelsson, Karl
dc.contributor.authorMarkus, Hugh S
dc.contributor.orcidTraylor, Matthew [0000-0001-6624-8621]
dc.contributor.orcidHowson, Joanna [0000-0001-7618-0050]
dc.contributor.orcidMarkus, Hugh [0000-0002-9794-5996]
dc.date.accessioned2018-09-08T06:34:17Z
dc.date.available2018-09-08T06:34:17Z
dc.date.issued2018
dc.description.abstractBackground and Purpose- Observational studies have reported increased risk of ischemic stroke among individuals with low serum 25-hydroxyvitamin D (S-25OHD) concentrations but uncertainty remains about the causality of this association. We sought to determine whether S-25OHD concentrations are causally associated with ischemic stroke and its subtypes using Mendelian randomization. Methods- We used summary-level data for ischemic stroke (34 217 cases and 404 630 noncases) from the MEGASTROKE consortium. As instruments, we used 6 single nucleotide polymorphisms, explaining 7.5% of the variance in S-25OHD, previously identified to be associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium (n=79 366). The analyses were conducted using the inverse-variance-weighted method and complemented with the weighted median, heterogeneity-penalized, and Mendelian randomization-Egger approaches. Results- Genetically higher S-25OHD concentration was not associated with ischemic stroke. The odds ratios (95% CI) per genetically predicted 1-SD (≈18 nmol/L) increase in S-25OHD concentrations, based on all 6 single nucleotide polymorphisms, were 1.01 (0.94-1.08; P=0.84) for all ischemic stroke, 0.94 (0.80-1.11; P=0.49) for large artery stroke, 0.95 (0.82-1.11; P=0.55) for small vessel stroke, and 1.02 (0.90-1.16; P=0.74) for cardioembolic stroke. The results were similar in sensitivity analyses. Conclusions- These findings provide no support that higher S-25OHD concentrations are causally associated with any ischemic stroke subtype. Thus, vitamin D supplementation will unlikely reduce the risk of ischemic stroke in the general population.
dc.description.sponsorshipThis work was supported by the Swedish Research Council for Health, Working Life and Welfare and the Swedish Brian Foundation. Hugh Markus is supported by a National Institute for Health Research Senior Investigator award, and his and Matthew Traylor’s work is supported by infrastructural support from the Cambridge University Hospitals Trust National Institute for Health Research Biomedical Research Centre.
dc.format.mediumPrint
dc.identifier.doi10.17863/CAM.27275
dc.identifier.eissn1524-4628
dc.identifier.issn0039-2499
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279907
dc.languageeng
dc.language.isoeng
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.publisher.urlhttp://dx.doi.org/10.1161/strokeaha.118.022242
dc.subject25-hydroxyvitamin D
dc.subjectpolymorphisms, single nucleotide
dc.subjectrandom allocation
dc.subjectstroke
dc.subjectvitamin D
dc.titleSerum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes A Mendelian Randomization Study
dc.typeArticle
dcterms.dateAccepted2018-07-24
prism.endingPage2511
prism.issueIdentifier10
prism.publicationDate2018
prism.publicationNameSTROKE
prism.startingPage2508
prism.volume49
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
rioxxterms.licenseref.startdate2018-10
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1161/STROKEAHA.118.022242

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