Causal relationship between human blood omega-3 fatty acids and the risk of epilepsy: A two-sample Mendelian randomization study

BACKGROUND: Though omega-3 fatty acids reduce seizures in several animal models, considerable controversy exists regarding the association between omega-3 fatty acids and epilepsy in human. OBJECTIVE: To assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis by applying summary statistics of genome-wide association study datasets of both exposure and outcomes. Single nucleotide polymorphisms significantly associated with blood omega-3 fatty acids levels were selected as instrumental variables to estimate the causal effects on epilepsy. Five MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) were conducted as the complement to IVW. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. RESULTS: Genetically predicted the increase of human blood omega-3 fatty acids levels was associated with a higher risk of epilepsy (OR = 1.160, 95%CI = 1.051–1.279, P = 0.003). CONCLUSIONS: This study revealed a causal relationship between blood omega-3 fatty acids and the risk of epilepsy, thus providing novel insights into the development mechanism of epilepsy.