Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes A Mendelian Randomization Study
Larsson, Susanna C
Howson, Joanna MM
Markus, Hugh S
Ovid Technologies (Wolters Kluwer Health)
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Larsson, S. C., Traylor, M., Mishra, A., Howson, J. M., Michaelsson, K., & Markus, H. S. (2018). Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes A Mendelian Randomization Study. STROKE, 49 (10), 2508-2511. https://doi.org/10.1161/STROKEAHA.118.022242
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.
MEGASTROKE Project of the International Stroke Genetics Consortium, Humans, Brain Ischemia, Vitamin D, Risk Factors, Phenotype, Polymorphism, Single Nucleotide, Stroke
This 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.
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
External DOI: https://doi.org/10.1161/STROKEAHA.118.022242
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279907