Modifiable risk factors for intracranial aneurysms: Evidence from genetic studies

Background: Intracranial aneurysm (IA) is a crucial health concern with limited strategies for prevention and treatment. Aim: To identify potentially modifiable risk factors, such as socioeconomic, behaviors, dietary, and cardiometabolic factors, for IA and its subtypes. Methods: Summary statistics for IA were derived from a genome-wide association study with an overall 79,429 participants. Single nucleotide polymorphisms associated with modifiable risk factors at genome-wide significance ( P = 5 × 10 –8 ) were used as instrumental variables. The inverse-variance-weighted method, weighted-median method, Mendelian randomization (MR)-Egger regression, MR-Pleiotropy RESidual Sum and Outlier, and multivariable MR analyses were performed to evaluate the effect estimates. Results: Genetically predicted educational attainment, insomnia, smoking, and systolic and diastolic blood pressure (SBP and DBP) were significantly associated with the risk of IA. The odds ratios (ORs) were 0.44 (95% confidence interval (CI): 0.37–0.52) for educational attainment, 1.15 (95% CI: 1.08–1.23) for insomnia, 1.56 (95% CI: 1.38–1.75) for smoking initiation, 2.69 (95% CI: 1.77–4.07) for cigarette per day, 2.65 (95% CI: 1.72–4.08) for lifetime smoking, 1.07 (95% CI: 1.06–1.09), and 1.06 (95% CI: 1.04–1.10) for SBP and DBP, respectively. Similar effect estimates were observed for unruptured IAs and aneurysmal subarachnoid hemorrhage. Conclusions: This study provided genetic evidence that several modifiable risk factors, including blood pressure, smoking, educational attainment, and insomnia were associated with the risk of IA.