Causal effect of psychiatric disorders on epilepsy: A two‐sample Mendelian randomization study

BACKGROUND: This study aims to explore the relationship between psychiatric disorders and the risk of epilepsy using Mendelian randomization (MR) analysis. METHODS: We collected summary statistics of seven psychiatric traits from recent largest genome‐wide association study (GWAS), including major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and insomnia. Then, MR analysis estimates were performed based on International League Against Epilepsy (ILAE) consortium data (n (case) = 15,212 and n (control) = 29,677), the results of which were subsequently validated in FinnGen consortium (n (case) = 6260 and n (control) = 176,107). Finally, a meta‐analysis was conducted based on the ILAE and FinnGen data. RESULTS: We found significant causal effects of MDD and ADHD on epilepsy in the meta‐analysis of the ILAE and FinnGen, with corresponding odds ratios (OR) of 1.20 (95% CI 1.08–1.34, p = .001) and 1.08 (95% CI 1.01–1.16, p = .020) by the inverse‐variance weighted (IVW) method respectively. MDD increases the risk of focal epilepsy while ADHD has a risk effect on generalized epilepsy. No reliable evidence regarding causal effects of other psychiatric traits on epilepsy was identified. CONCLUSIONS: This study suggests that major depressive disorder and attention deficit hyperactivity disorder may causally increase the risk of epilepsy.