The relationship between metabolites and gout: a Mendelian randomization study

Background: Gout is closely tied to metabolism, yet there is limited evidence on how metabolites may cause or prevent the condition. Methods: This study utilized a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 1,400 serum metabolites and gout. We primarily employed the inverse variance-weighted (IVW) method to estimate causal effects, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode for comprehensive evaluations. Additionally, we conducted tests for pleiotropy and heterogeneity. Results: After a rigorous selection process, we identified eight known metabolites and four unknown metabolites associated with gout. Among the eight known metabolites, Glucuronide of piperine metabolite C17H21NO3 and the Phosphate to mannose ratio were positively associated with an increased risk of gout. Conversely, levels of 5 alpha-androstan-3 beta, 17 alpha-diol disulfate, Pantoate, N-carbamoylalanine, Sphingomyelin (d18:0/20:0, d16:0/22:0), Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH)), and Mannose were linked to a decreased risk of gout. Conclusion: This study identified eight metabolites from 1,400 blood samples significantly linked to gout risk. Integrating genomics and metabolomics offers valuable insights for gout screening and prevention, indicating that specific blood metabolites can help identify individuals at higher risk.