Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian...

Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy.

Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy.

After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 ∼ 1.06,P = 2.55 × 10^-4), IgD⁺CD38^dim (OR = 1.05, 95 % CI = 1.02 ∼ 1.08, P = 4.73 × 10^-4), CD24⁺CD27⁺ (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 4.82 × 10^-4), and IgD^-CD38^dim (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 1.04 × 10^-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy.

This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.