Modifiable risk factors for intracranial aneurysms: Evidence from genetic studies

Abstract

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.

Predicting the causal relationship between polyunsaturated fatty acids and cerebral aneurysm risk from a Mendelian randomization study

“…Third, we clustered SNPs in linkage disequilibrium (LD, R2≥0.001 and within 10 mb). Fourth, to eliminate unclear, palindromic and associated with known confounding factors (body mass index (McDowell et al, 2018), blood pressure (Sun et al, 2022), type 2 diabetes (Tian et al, 2022), high-density lipoprotein (Huang et al, 2018)) SNPs. Fifth, If an instrumental SNP for the exposure was not available from the outcome data set, we replaced it with a suitable proxy SNP (r 2 >0.8 in the European 1000 Genomes Project reference panel using LDlink https://ldlink.nci.nih.gov/]) or removed it in the absence of such a proxy.…”

Predicting the causal relationship between polyunsaturated fatty acids and cerebral aneurysm risk from a Mendelian randomization study

“…Third, we clustered SNPs in linkage disequilibrium (LD, R2≥0.001 and within 10 mb). Fourth, to eliminate unclear, palindromic and associated with known confounding factors (body mass index (McDowell et al, 2018 ), blood pressure (Sun et al, 2022 ), type 2 diabetes (Tian et al, 2022 ), highdensity lipoprotein (Huang et al, 2018 )) SNPs. Fifth, If an instrumental SNP for the exposure was not available from the outcome data set, we replaced it with a suitable proxy SNP (r 2 >0.8 in the European 1000 Genomes Project reference panel using LDlink https://ldlink.nci.nih.gov/ ]) or removed it in the absence of such a proxy.…”

Early sexual activity lowers the incidence of intracranial aneurysm: a Mendelian randomization investigation

“…This helps alleviate concerns related to potential confounding and the reversal of causation ( 8 ). In contemporary times, numerous MR studies on intracranial aneurysms have emerged, contributing valuable clinical evidence ( 9 , 10 ). This highlights that MR serves as a reliable research method capable of addressing diverse inquiries.…”