Assessing the causal association between human blood metabolites and the risk of gout

The occurrence of gout is closely related to metabolism, but there is still a lack of evidence on the causal role of metabolites in promoting or preventing gout.We applied a two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and gout using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. We also performed a metabolic pathway analysis to identify potential metabolic pathways.After screening, 486 metabolites were retained for MR analysis. After screening by IVW and sensitivity analysis, 14 metabolites were identified with causal effect on gout (P < 0.05), among which hexadecanedioate was the most significant candidate metabolite associated with a lower risk of gout (IVW OR = 0.50; 95% CI = 0.38-0.67; P = 1.65 × 10-6 ). Metabolic pathway analysis identified one pathway that may be associated with the disease.This MR study combining genomics with metabolomics provides a novel insight into the causal role of blood metabolites in the risk of gout, which implies that examination of certain blood metabolites would be a feasible strategy for screening populations with a higher risk of gout.