The association between immune cells and epilepsy：Evidence from Mendelian randomization study and meta-analysis

Epilepsy is one of the most common serious brain diseases, affecting more than 70 million people. Complex immune-brain interactions can affect the development and function of epilepsy.Two-sample Mendelian randomized (MR) analysis was used to determine the causal relationship between 731 immune cells as exposure data and epilepsy, focal epilepsy (FE), and generalized epilepsy(GE) as outcome data based on the Genome-Wide Association Studies (GWAS) and Finngen R10 dataset. The main methods to evaluate causality were inverse variance weighted (IVW) and P < 0.05 was included in the primary results. Comprehensive sensitivity analyses were used to verify the robustness of results. Finngen R10 dataset and GWAS dataset was respectively used as discovery dataset and validation dataset to select common positive immune cell phenotypes. Finally, reverse MR analysis and meta-analysis were conducted to obtain more accurate results. The final results showed that CD19 on IgD + CD38- is the risk factor for epilepsy (P = 0.031 in the discovery dataset; P = 0.032 in the validation dataset) and CD38 on CD20- (P = 0.007 in the discovery dataset; P = 0.035 in the validation dataset) and CD64 on CD14 + CD16- monocyte (P = 0.019 in the discovery dataset; P = 0.020 in the validation dataset) respectively served as protective factor and risk element for GE based on two different datasets. The meta-analysis of the IVW results from both datasets further support the causal effects of CD19 on IgD + CD38- on epilepsy (odds ratio (OR) = 1.037,95% confidence interval (CI) = 1.012–1.063, P = 0.003), CD38 on CD20- on GE (OR = 0.877,95%CI = 0.777–0.989, P = 0.032) and CD64 on CD14 + CD16- monocyte on GE (OR = 1.044,95%CI = 1.017–1.071, P = 0.001).