Educational attainment protects against epilepsy independent of cognitive function: A Mendelian randomization study.

OBJECTIVE Observational studies have suggested that increased levels of education and cognition are associated with a reduced risk of epilepsy. However, such associations are easily influenced by confounding or reverse causality. Hence, we conducted a two-sample univariable and multivariable Mendelian randomization (MR) to estimate the total and independent causal effects of educational attainment and cognition on epilepsy risk. METHODS We performed MR estimates on International League Against Epilepsy (ILAE) Consortium genome-wide association study (GWAS) data (15 212 epilepsy cases and 29 677 controls). We then validated the results in FinnGen (3424 epilepsy cases and 110 963 controls) and applied meta-analysis to all the results. RESULTS In the meta-analysis of the ILAE and FinnGen results, genetically determined increased educational attainment was associated with a reduced risk of epilepsy (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.80-0.88; P < .001). Similarly, genetically determined increased cognitive function was associated with a reduced risk of epilepsy (OR 0.94, 95% CI 0.88-1.00, P = .043). When educational attainment and cognitive function were included in the same multivariable MR, only educational attainment was still associated with a reduced risk of epilepsy (OR 0.88, 95% CI 0.81-0.95, P = .002). SIGNIFICANCE This MR study provides evidence to support that increased educational attainment can reduce the risk of developing epilepsy independent of cognitive function.