Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study. Issue 10 (October 2018)

• Record Type: Journal Article
• Authors: Larsson, Susanna C.; Traylor, Matthew; Mishra, Aniket; Howson, Joanna M.M.; Michaëlsson, Karl; Markus, Hugh S.
• Is Part Of: Stroke. Volume 49:Issue 10(2018)
• Publication Date: 2018-10
• Subjects: 25-hydroxyvitamin D -- polymorphisms, single nucleotide -- random allocation -- stroke -- vitamin D; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.118.022242
• Languages: English
• ISSNs: 0039-2499

Abstract

Abstract : Background 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. Abstract : Supplemental Digital Content is available in the text.