Understanding the effect of educational attainment on the risk of retinal detachment: a Mendelian randomization mediation analysis

Abstract Purpose Higher educational attainment is generally associated with better health outcomes, but paradoxically, some evidence suggests an increased risk of rhegmatogenous retinal detachment (RD) among individuals with higher education, potentially due to myopia. This study aimed to investigate whether the association between education and RD is causal and to what extent it is mediated by refractive error and other modifiable lifestyle factors. Methods We conducted univariable and multivariable Mendelian randomization (MR) analyses using publicly available genome-wide association study summary statistics from up to 3 million individuals of European ancestry. Genetically predicted educational attainment was examined for its effect on RD risk. MR mediation analysis was employed to estimate the contribution of refractive error, smoking, alcohol consumption, and body mass index (BMI) to the observed association. Results Each one standard deviation increase in genetically predicted educational attainment was associated with a 1.50-fold higher risk of RD (95% confidence interval [CI]: 1.02–2.21; p = 0.04). MR mediation analysis suggested that the effect of education on RD was largely mediated by refractive error. Adjustments for smoking, alcohol use, and BMI showed limited impact on the association, reinforcing myopia as the principal mediator. Conclusions Our findings provide evidence consistent with a possible causal effect between higher educational attainment and increased RD risk, driven predominantly by myopia. These results highlight the potential importance of refractive error as a pathway linking educational attainment and RD, which may be relevant for future prevention strategies.