Mendelian randomization study shows no causal effects of serum urate levels on the risk of MS

OBJECTIVE: To examine whether lifelong genetically increased serum urate levels, a potent antioxidant, contribute to MS susceptibility using Mendelian randomization (MR). METHODS: This 2-sample MR study included 25 independent genetic variants strongly associated with serum urate levels in a genome-wide association study meta-analysis of 140,949 individuals. Effects on the risk of MS were assessed with summary statistics from 3 large-scale MS genetic data sets totaling 61,667 MS cases and 86,806 controls from the International MS Genetic Consortium. Multiple sensitivity analyses were performed to evaluate the assumptions of MR and remove potentially pleiotropic variants. RESULTS: Using inverse-variance weighted MR, we found no evidence for a causal effect of serum urate level on the risk of MS in any of the cohorts (MS1: OR 0.99 per each mg/dL unit increase in urate, 95% CI 0.89–1.08, p = 0.76; MS2: OR = 0.99, 95% CI 0.89–1.11, p = 0.90; MS3: OR = 1.00, 95% CI 0.98–1.2, p = 0.91). Pleiotropy robust MR methods yielded consistent estimates. CONCLUSION: This MR study does not support a clinically relevant causal effect of serum urate levels on the risk of MS.