Abstract
BACKGROUND: Epilepsy is a severe neurological disorder characterized by persistent seizures and, in some patients, associated neurobiological, cognitive, and psychosocial consequences. It is influenced by various genetic factors, including the Ephrin-B2 (EFNB2) gene. METHODS: This study utilized bidirectional Mendelian randomization (MR) to explore the potential causal relationship between serum levels of EFNB2 and epilepsy using data from extensive genome-wide association studies (GWAS). We selected serum levels of EFNB2 and generalized epilepsy traits, applying strict criteria for instrumental variables to ensure validity and mitigate confounding influences. The analysis included sensitivity tests like the MR pleiotropy residuals and outliers test, as well as co-localization to evaluate shared genetic influences. RESULTS: Our results indicated a significant causal relationship between serum levels of EFNB2 and epilepsy, suggesting that EFNB2 could be involved in the pathogenesis of epilepsy through mechanisms that may not be directly linked to shared genetic pathways. CONCLUSION: These results suggest a potential association between EFNB2 and epilepsy, highlighting the need for further studies to clarify its role and explore its possible relevance as a therapeutic target.