The associations between oxidative stress and epilepsy: a bidirectional two-sample Mendelian randomization study.

Background: Studies on the association between oxidative stress and epilepsy have yielded varied results. In this study, we aimed to investigate the causal relationship between oxidative stress markers and epilepsy.

Methods: A bidirectional two-sample Mendelian randomization (MR) study was performed based on publicly available statistics from genome-wide association studies. To explore the causal effects, single nucleotide polymorphisms were selected as instrumental variables. Inverse-variance weighted method was performed for primary analysis, supplemented by weighted median, MR-Egger, simple mode, and weighted mode. Furthermore, sensitivity analyses were performed to detect heterogeneity and pleiotropy.

Results: Our results showed that part of the oxidative stress biomarkers are associated with epilepsy and its subtypes. Zinc is associated with increased risk of epilepsy and generalized epilepsy (odds ratio [OR] = 1.064 and 1.125, respectively). Glutathione transferase is associated with increased risk of generalized epilepsy (OR = 1.055), while albumin is associated with decreased risk of generalized epilepsy (OR = 0.723). Inverse MR analysis revealed that epilepsy is associated with increased levels of uric acid and total bilirubin (beta = 1.266 and 0.081, respectively), as well as decreased zinc level (beta =  - 0.278). Furthermore, generalized epilepsy is associated with decreased ascorbate and retinol levels (beta =  - 0.029 and - 0.038, respectively).

Conclusions: Our study presented novel evidence of potential causal relationships between oxidative stress and epilepsy, suggesting potential therapeutic targets for epilepsy.