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

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.

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.

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).

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