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

Abstract

BackgroundThough 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.ObjectiveTo assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes.MethodsWe 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.ResultsGenetically 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).ConclusionsThis 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.