Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes

Area of Science:

• Genetics
• Neurology
• Endocrinology

Background:

• Observational studies suggest a link between low serum 25-hydroxyvitamin D (S-25OHD) and increased ischemic stroke risk.
• Causality of this association remains uncertain.

Purpose of the Study:

• To investigate the causal association between genetically predicted S-25OHD concentrations and ischemic stroke, including its subtypes.

Main Methods:

• Mendelian randomization analysis using summary-level data from MEGASTROKE (34,217 cases, 404,630 noncases).
• Employed 6 single nucleotide polymorphisms associated with S-25OHD as instrumental variables.
• Utilized inverse-variance-weighted, weighted median, and other sensitivity analyses.

Main Results:

• Genetically predicted higher S-25OHD concentrations were not causally associated with ischemic stroke or its subtypes (large artery, small vessel, cardioembolic).
• Odds ratios per 1-SD increase in S-25OHD were consistently near 1.0 across all stroke types and subtypes.
• Sensitivity analyses confirmed these findings.

Conclusions:

• The study provides no evidence for a causal role of S-25OHD concentrations in ischemic stroke.
• Vitamin D supplementation is unlikely to be an effective strategy for reducing ischemic stroke risk in the general population.