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

• Type of Material: Article
• Authors: Hyacinth Idu Hyacinth, Emory University; Adolfo Correa, Emory University; Susanna C. Larsson, Karolinska Institutet; Matthew Traylor, Stroke Research Group; Stephen Burgess, MRC Biostatistics Unit; Giorgio B. Boncoraglio, Foundation IRCCS Neurological Institute; Christina Jern, Göteborg University; Karl Michaëlsson, Uppsala Universitet; Hugh S. Markus, Stroke Research Group
• Language: English
• Date: 2019-02-26
• Publisher: American Academy of Neurology (AAN)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 American Academy of Neurology.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1212/WNL.0000000000007001
• Title of Journal or Parent Work: Neurology
• ISSN: 0028-3878
• Volume: 92
• Issue: 9
• Start Page: E944
• End Page: E950
• Grant/Funding Information: This work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council.; Hugh Markus is supported by an NIHR Senior Investigator award. His and Matthew Traylor's work is supported by infrastructural support from the Cambridge University Hospitals Trust NIHR Biomedical Research Centre.
• Research Categories: Biology, Neuroscience; Biology, Biostatistics

Abstract

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.