Epilepsy and systemic autoimmune diseases: A bidirectional two‐sample Mendelian randomization study

OBJECTIVE: Epidemiological data indicates that individuals with epilepsy exhibit an elevated susceptibility to autoimmune disorders, and conversely, those with systemic autoimmune diseases (SAD) demonstrate a heightened predisposition to epilepsy. Although an increasing number of publications support this association, the causal direction remains undetermined. This investigation offers evidence supporting a causal relationship between these conditions through a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Bidirectional two-sample MR analyses were performed to investigate the causal relationships and directionality between various epilepsy subtypes and eight SAD. The analysis utilized genome-wide association study (GWAS) summary data for the following conditions: type 1 diabetes, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis, coeliac disease, multiple sclerosis (MS), ulcerative colitis, and Crohn's disease. RESULTS: In this study, causal analyses were performed for different epilepsy subtypes and SAD disorders. In the Inverse-Variance Weighted (IVW) model, the MR study indicated that focal epilepsy increased the risk of IBD [odds ratio (OR): 1.15, confidence interval (CI): 1.02-1.30, p: 0.027] and MS [OR: 1.25, CI: 1.07-1.47, p: 0.004]. Childhood absence epilepsy increased the risk of MS [OR: 0.25, CI: 0.07-0.90, p: 0.034]. Reverse analyses showed that SLE increased the risk of myoclonic epilepsy in adolescents [OR: 1.01, CI: 1.00-1.01, p: 0.042], and IBD [OR: 0.99, CI: 0.99-1.00, p: 0.013], and celiac disease [OR: 0.99, CI: 0.99-1.00, p: 0.021] reduced the risk of generalized epilepsy. The results demonstrated homogeneity, and the MR-Egger directions were concordant. SIGNIFICANCE: This study shows that epilepsy is a causal risk factor for both IBD and MS, providing new insights into the prevention of SAD in people with epilepsy. PLAIN LANGUAGE SUMMARY: This paper employs a bidirectional two-sample MR analysis to investigate the genetic correlation between epilepsy and autoimmune diseases, revealing potential associations between the onset of epilepsy and MS as well as IBD. Further exploration in this area requires support from clinical data.