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.