Susanna C Larsson1, Dipender Gill2. 1. From the Unit of Cardiovascular and Nutritional Epidemiology (S.C.L.), Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Unit of Medical Epidemiology (S.C.L.), Department of Surgical Sciences, Uppsala University, Sweden; Department of Epidemiology and Biostatistics (D.G.), School of Public Health, St Mary's Hospital, Imperial College London; Clinical Pharmacology and Therapeutics Section (D.G.), Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London; Clinical Pharmacology Group (D.G.), Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London; and Novo Nordisk Research Centre Oxford (D.G.), UK. susanna.larsson@ki.se. 2. From the Unit of Cardiovascular and Nutritional Epidemiology (S.C.L.), Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Unit of Medical Epidemiology (S.C.L.), Department of Surgical Sciences, Uppsala University, Sweden; Department of Epidemiology and Biostatistics (D.G.), School of Public Health, St Mary's Hospital, Imperial College London; Clinical Pharmacology and Therapeutics Section (D.G.), Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London; Clinical Pharmacology Group (D.G.), Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London; and Novo Nordisk Research Centre Oxford (D.G.), UK.
Abstract
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.
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.