Modifiable risk factors for intracranial aneurysms in Asian populations: A univariable and multivariable Mendelian randomization study

Abstract

Background: To investigate the potential modifiable risk factors for intracranial aneurysms in Asian populations using Mendelian randomization analysis.

Methods: Genetic data for intracranial aneurysms and modifiable risk factors in Asian populations were extracted from the IEU Open GWAS project database. Single-nucleotide polymorphisms significantly associated with modifiable risk factors across the genome were used as instrumental variables. Two-sample and multivariate Mendelian randomization analyses were performed to assess the causal relationship between each risk factor and intracranial aneurysms.

Results: In Asian populations, univariable MR analysis revealed that genetically predicted systolic blood pressure, diastolic blood pressure, and ischemic stroke were significantly associated with an increased risk of intracranial aneurysms (OR = 6.14, 95% CI: 3.67-10.26, P = 4.45 × 10^-12; OR = 4.88, 95% CI: 2.69-8.86, P = 1.97 × 10^-7; OR = 1.89, 95% CI: 1.28-2.78, P = 1.38 × 10^-3), while serum low-density lipoprotein cholesterol, total cholesterol, and type 2 diabetes mellitus were significantly associated with a decreased risk of intracranial aneurysms (OR = 0.65, 95% CI: 0.50-0.84, P = 1.13 × 10^-3; OR = 0.62, 95% CI: 0.49-0.79, P = 6.90 × 10^-5; OR = 0.82, 95% CI: 0.76-0.89, P = 3.48 × 10^-7). Multivariate MR analysis showed that systolic blood pressure (OR = 12.33, 95% CI: 2.46-61.74, P = 2.24 × 10^-3), ischemic stroke (OR = 1.50, 95% CI: 1.01-2.12, P = 4.78 × 10^-2), and type 2 diabetes mellitus (OR = 0.79, 95% CI: 0.70-0.89, P = 1.11 × 10^-4) remained significant causal factors for intracranial aneurysms.

Conclusions: In Asian populations, there is a causal relationship between systolic blood pressure, ischemic stroke, and an increased risk of intracranial aneurysms, while type 2 diabetes mellitus is associated with a decreased risk of intracranial aneurysms.