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Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study.

TitleSerum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study.
Publication TypeJournal Article
Year of Publication2019
AuthorsLarsson SC, Traylor M, Burgess S, Boncoraglio GB, Jern C, Michaëlsson K
Secondary AuthorsMarkus HS
Corporate AuthorsMEGASTROKE project of the International Stroke Genetics Consortium
Date Published2019 02 26
KeywordsBrain Ischemia, Calcium, Humans, Intracranial Embolism, Magnesium, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Stroke

OBJECTIVE: To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.

METHODS: Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).

RESULTS: In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; = 1.3 × 10) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; = 1.6 × 10) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.

CONCLUSIONS: This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

Alternate JournalNeurology
PubMed ID30804065
PubMed Central IDPMC6404465
Grant ListMC_UU_00002/7 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom