Causal relationships between ischemic stroke and epilepsy: a Mendelian randomization study

Background: Epidemiological evidence suggests that ischemic stroke may increase the risk of epilepsy. However, the causal relationship between these two conditions is currently inconclusive. We aimed to elucidate the possible causal relationship between ischemic stroke and related subtypes of epilepsy by a two-sample Mendelian randomization (MR) analysis. Methods We extracted 11 single nucleotide polymorphisms (SNPs) significantly associated with ischemic stroke from a large genomic association study (GWAS) of European individuals (440328 individuals) as instrumental variables and used the GWAS of epilepsy-related subtypes provided by the International League Against Epilepsy as an outcome data source. Inverse variance weighting (IVW) was used as the primary method to assess effect estimates. Sensitivity analysis was performed using weighted median, MR-Egger and MR-PRESSO to assess heterogeneity and pleiotropy. Results In the IVW random-effects model, 11 SNPs were used as instrumental variables, and a significant causal relationship was found between genetic susceptibility to ischemic stroke and generalized epilepsy (OR, 1.24; 95% confidence interval (CI), 1.09, 1.42; P = 0.0009). The results of the weighted median and MR-Egger methods were in general agreement. Sensitivity analysis showed no heterogeneity or polymorphism. Reverse MR analysis failed to detect a causal relationship between generalized epilepsy and ischemic stroke. In addition, we found no causal relationship between ischemic stroke and focal epilepsy (OR, 1.06; 95% confidence interval (CI), 0.93, 1.20; P = 0.3957). Conclusion There is a causal relationship between ischemic stroke and the occurrence of generalized epilepsy, but not with focal epilepsy.