Genetic association between years of education and intracranial aneurysm: A two-sample Mendelian randomization study.

OBJECTIVE: To investigate whether genetically proxied educational attainment influences the risk of intracranial aneurysm. METHOD: We conducted a two-sample Mendelian randomization analysis using genome wide association study summary statistics from individuals of European ancestry. The inverse variance weighted method was the primary estimator, complemented by MR Egger, weighted median, weighted mode, and simple mode analyses, with years of schooling and college completion as educational exposures combined with intracranial aneurysm GWAS data. RESULTS: We selected two groups of genes associated with genetic susceptibility to education as exposure factors. When using years of education from the UK Biobank based GWAS as the exposure, the inverse variance weighted method indicated an inverse association between genetically proxied longer schooling and intracranial aneurysm risk. MR Egger regression suggested that directional pleiotropy was unlikely to strongly bias the results and yielded an inverse association between years of schooling and intracranial aneurysm. The weighted median estimator yielded a similar direction and magnitude of effect. When using college completion as the exposure, the inverse variance weighted method also indicated an inverse association with intracranial aneurysm risk, and sensitivity analyses produced estimates of similar direction and magnitude. MR-Egger regression intercept testing did not provide evidence of substantial directional pleiotropy. CONCLUSION: These Mendelian randomization findings are consistent with a potentially protective association of higher genetically proxied educational attainment with intracranial aneurysm risk in individuals of European ancestry.