Association of Serum Magnesium Levels With Risk of Intracranial Aneurysm: A Mendelian Randomization Study.

Objective Magnesium has been implicated in regulating blood pressure and vascular endothelial cell function, but its role in the pathophysiology of intracranial aneurysm is not known. Here we performed a Mendelian randomization analysis to investigate the association between serum magnesium concentration and risk of intracranial aneurysm. Methods Five single-nucleotide polymorphisms strongly associated with serum magnesium concentrations in a genome-wide association study in 23,829 individuals of European ancestry were used as genetic instruments. Genetic association estimates for intracranial aneurysm were obtained from a genome-wide association study in 79,429 individuals (7,495 cases and 71,934 controls). The inverse variance weighted method was used in the primary analyses to obtain the causal estimates. Results Higher genetically predicted serum magnesium concentrations were associated with lower risk of intracranial aneurysm. The odds ratios per 0.1 mmol/L increment in genetically predicted serum magnesium concentrations were 0.66 (95% confidence interval [CI] 0.49–0.91) for intracranial aneurysm (unruptured and ruptured combined), 0.57 (95% CI 0.30–1.06) for unruptured intracranial aneurysm, and 0.67 (95% CI 0.48–0.92) for aneurysmal subarachnoid hemorrhage. Conclusion This study provides evidence to support that increased serum magnesium concentrations reduce the risk of intracranial aneurysm and associated hemorrhage.