Assessment of bidirectional relationships between multiple sclerosis and epilepsy: A two-sample Mendelian randomization study

Abstract

Background and objective: Epidemiological studies indicate that multiple sclerosis (MS) is associated with epilepsy. However, the causality and directionality of this association remain under-elucidated. This study aimed to reveal the causality between MS and epilepsy.

Methods: A two-sample Mendelian randomization (MR) analysis was performed by using summarized statistics derived from large genome-wide association studies of MS and epilepsy. We used the inverse variance weighted method as the primary approach, and then four other MR methods to bidirectionally evaluate the causality of the association between MS and epilepsy. Additional sensitivity analyses were performed to measure the robustness of the findings.

Results: Genetically predicted MS was positively correlated with developing all epilepsy [odds ratio (OR) = 1.027 (1.003-1.051), P = 0.028] and generalized epilepsy [OR = 1.050 (1.008-1.094), P = 0.019]. In the reverse MR analysis, all epilepsy [OR = 1.310 (1.112-1.543), P = 0.001], generalized epilepsy [OR = 1.173 (1.010-1.363), P = 0.037], and focal epilepsy [OR = 1.264 (1.069-1.494), P = 0.006] elevated the risk of developing MS. The result remained robust and congruous across all sensitivity analyses conducted.

Conclusions: MS is potentially associated with a higher risk of developing epilepsy. Furthermore, epilepsy may be a causal determinant of MS risk. These findings may further the understanding of the interaction of the two conditions.

Keywords: Epilepsy; GWAS; Inflammation; Mendelian randomization; Multiple sclerosis.