A causal association between gout and uric acid levels and the risk of epilepsy and its subtypes: a two-sample Mendelian randomization study

Objective: Gout and Uric acid levels have been investigated in observational studies with epilepsy risk; however, the results were inconsistent. Therefore, we conducted a Mendelian randomization (MR) study to assess the causality of these relationships. Methods: To explore the causal relationship and ascertain specific Gout and Uric acid for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on data from the Epilepsy Genome-wide Association Study (GWAS) provided by the International League Against Epilepsy. The GWAS summary statistics for Gout were generated by the FINNGEN consortium and GWAS data of Uric acid from the Bio-Bank Japan (BBJ). The main analytical method for evaluating causality was the inverse-variance weighted (IVW) approach. To complement the IVW method, we also applied three additional MR methods: MR-Egger, and weighted median. Additionally, because the number of SNP-s screened out is relatively small in this study, so there may be weak instrumental variables, and MR-RAPS is a method that specifically deals with weak instrumental variables and exists to assist the results generated by IVW. Results: Genetically predicted Gout was associated with a higher risk of epilepsy (OR:1.014, CI:1.011-1.017, P<0.0001)、Generalized epilepsy (OR:1.009, CI:1.000-1.018, P=0.0424) and Focal epilepsy (OR:1.033, CI:1.002-1.088, P=0.0407)in the European populations. Genetically predicted Uric acid levels was not related to epilepsy、generalized epilepsy and focal epilepsy in Europe and Gout and Uric acid levels were not related to epilepsy in East Asia. Our results suggest that gout has a detrimental effect on epilepsy risk、sensitivity analyses found no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. Conclusions: This is the first study to explore the potential causal relationship between gout、uric acid and epilepsy using MR Analysis. Through the MR study, we analyzed the causal relationship between gout and uric acid and epilepsy and identified specific ones associated with an increased risk of epilepsy. Our findings may provide useful biomarkers for disease progression in epilepsy and candidates for potential therapeutic targets. In addition, our study highlights the importance of conducting genetic association studies in diverse populations to fully understand the genetic and environmental interactions of complex diseases.