CAUSAL ROLES OF SERUM URIC ACID LEVELS AND GOUT IN SEPSIS: A MENDELIAN RANDOMIZATION STUDY

Objective: Several epidemiological studies have identified a potential link between serum uric acid (UA), gout, and sepsis. The primary objective of this study is to delve deeper into this connection, investigating the causal effect of UA and gout on sepsis by applying Mendelian randomization (MR). Methods: The causal relationship was analyzed using data from Genome-Wide Association Study (GWAS). Inverse variance weighting (IVW) was used as the main analysis method. Three complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple median method. Horizontal pleiotropy was identified by MR-Egger intercept test. Cochran's Q statistics were employed to assess the existence of instrument heterogeneity. The leave-one-out method was used as a sensitivity analysis. Results: The IVW results indicated that there was a positive causal relationship between UA and sepsis (critical care) (odds ratio [OR] = 0.24, 95% confidence interval [CI]: 0.04 to 0.43, P = 0.018, F = 4,291.20). There was no significant association between UA and sepsis (28-day death in critical care) (OR = 0.10, 95% CI = -0.29 to 0.50, P = 0.604). There was no significant association between gout and sepsis (critical care) (OR = 0.85, 95% CI = -4.87 to 6.57, P = 0.771), and sepsis (28-day death in critical care) (OR = -6.30, 95% CI = -17.41 to 4.81, P = 0.267). Horizontal pleiotropy was absent in this study. The results were robust under all sensitivity analyses. Conclusion: The study revealed that elevated UA levels were causally linked with sepsis (critical care). No causal relationship had been found between UA and sepsis (28-day death in critical care), as well as between gout and sepsis.