The impact of educational attainment on the risk of three types of atherosclerosis: A two-sample mendelian...

Atherosclerosis is a leading contributor to cardiovascular disease and mortality worldwide, influenced by both genetic and environmental factors. Educational attainment, as a key socioeconomic indicator, has been consistently associated with cardiovascular risk in observational studies. However, the causal nature of this relationship remains uncertain. This study aimed to investigate the potential causal association between educational attainment and the risk of atherosclerosis using Mendelian randomization (MR) methods.

We performed a two-sample MR analysis using genome-wide association study (GWAS) summary statistics. Educational attainment, measured as college completion and years of schooling, was used as the exposure, and atherosclerosis, coronary artery disease, and cerebral atherosclerosis were the outcomes. Causal estimates were obtained using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. Sensitivity analyses, including pleiotropy and heterogeneity tests, were conducted to validate the robustness of the results.

Using the inverse variance weighted (IVW) method, genetically predicted higher educational attainment (college completion) was associated with a lower risk of atherosclerosis (OR = 0.43, 95 % CI: 0.32-0.57, P = 1.79E-08) and coronary artery disease (OR = 0.57, 95 % CI: 0.46-0.71, P = 6.62E-07). Additionally, an inverse association was observed between genetically predicted years of education and coronary artery disease risk (OR = 0.95, 95 % CI: 0.93-0.97, P = 2.85E-06). No significant association was found with cerebral atherosclerosis (P > 0.05). Sensitivity analyses indicated no evidence of horizontal pleiotropy or substantial bias. Although the associations did not reach statistical significance in MR-Egger or weighted mode analyses, the odds ratios remained below 1 across these methods, suggesting consistent protective trends and supporting the robustness of the findings.

Our findings provide genetic evidence supporting a potential causal association between educational attainment and the risk of atherosclerosis, particularly coronary artery disease. These associations likely reflect indirect effects mediated by socioeconomic and behavioral pathways. Future research should investigate the mechanisms underlying these associations and explore how educational inequalities contribute to cardiovascular health disparities.