A two-sample Mendelian randomization analysis of modifiable risk factors and intracranial aneurysms

We aimed to investigate the causality between potentially modifiable risk factors and the risk of intracranial aneurysm. Genetic instruments for 51 modifiable factors and intracranial aneurysm data were obtained from recently published genome-wide association studies. We applied two-sample Mendelian randomization methods to investigate their causal relationships. Genetically predicted cigarettes per day, smoking initiation, systolic blood pressure, hypertension and body fat percentage were significantly associated with an increased risk of intracranial aneurysm [odds ratios (OR) 2.67, 95% confidence interval (CI) 1.75-4.07, p = 5.36 × 10^-6, OR 1.53, 95% CI 1.32-1.77, p = 9.58 × 10^-9, OR 1.05, 95% CI 1.02-1.08, p = 1.18 × 10^-3, OR 1.65, 95% CI 1.19-2.28, p = 2.56 × 10^-3 and OR 1.29, 95% CI 1.11-1.52, p = 1.33 × 10^-3, respectively]. Type 2 diabetes mellitus was significantly associated with a decreased risk of intracranial aneurysm (OR 0.89, 95% CI 0.83-0.95, p = 8.54 × 10^-4). Body fat percentage was significantly associated with subarachnoid haemorrhage (p = 5.70 × 10^-5). This study provided genetic evidence of causal effects of smoking, blood pressure, type 2 diabetes mellitus and obesity on the risk of intracranial aneurysm.