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

Susanna C. Larsson*, Matthew Traylor, groep, Stephen Burgess, Giorgio B. Boncoraglio, Christina Jern, Karl Michaëlsson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses 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).ResultsIn 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; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 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.ConclusionsThis 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.

Original languageEnglish
Pages (from-to)E944-E950
Issue number9
Publication statusPublished - 26 Feb 2019

Bibliographical note

Funding Information:
The Article Processing Charge was funded by the Swedish Research Council for Health, Working Life and Welfare (Forte).

Funding Information:
The authors thank the International Stroke Genetics Consortium for providing summary statistics data from the MEGASTROKE project. The MEGASTROKE authors are listed in the supplement. The MEGASTROKE project received funding from sources specified at

Publisher Copyright:
© 2019 American Academy of Neurology.


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