Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking,
coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits,
type 2 diabetes, systolic and diastolic blood pressure,
lipids, and
inflammation and kidney function markers) with risks of any (ruptured or unruptured)
intracranial aneurysm and
aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta-analyses of genome-wide association studies. The inverse-variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy.
Genetic predisposition to smoking,
insomnia, and higher blood pressure was associated with an increased risk of both
intracranial aneurysm and
aneurysmal subarachnoid hemorrhage. For
intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93-5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10-1.40) per unit increase in log-odds of
insomnia, and 2.92 (95% CI, 2.49-3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher
triglyceride levels, higher body mass index, and lower
low-density lipoprotein cholesterol levels with higher risk of
intracranial aneurysm and
aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking,
insomnia, and
high blood pressure are major risk factors for
intracranial aneurysm and
aneurysmal subarachnoid hemorrhage.