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

ABSTRACT

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.