To explore the relationship between uric acid and the risk of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD), providing new insights for the prevention of NAFLD.

Utilizing data from the 2017-2018 NHANES population and summary data from genome-wide association studies (GWAS), the association between uric acid and the risk of hepatic steatosis and NAFLD was analyzed using restricted cubic spline models, generalized linear models, and binary logistic regression models. The inverse variance weighted method was employed as the primary approach for Mendelian randomization (MR) analysis to assess the causal relationship between uric acid and NAFLD. Additional verification of results was conducted using MR Egger regression, weighted median methods, simple models, and weighted models, followed by sensitivity testing.

After adjusting for all covariates, a linear relationship was observed between uric acid and the risks of hepatic steatosis and NAFLD (P_non-linear > 0.05). Populations with higher uric acid levels exhibited increased risks of hepatic steatosis (β=3.559,95%CI: 1.722-5.395, P < 0.001) and NAFLD (OR=1.151, 95%CI: 1.048-1.265, P=0.003). The MR analysis using the inverse variance weighted method indicated a causal relationship between uric acid and NAFLD (OR=1.68, 95%CI: 1.01-2.81, P=0.049),with the other four analytical methods providing similar directional causal inferences. Sensitivity tests suggested no significant heterogeneity or horizontal pleiotropy among instrumental variables (P > 0.05), and the results were not influenced by individual genetic variations.

Uric acid is positively linearly correlated with the risk of hepatic steatosis and NAFLD, indicating that controlling uric acid levels may play a crucial role in the prevention and management of NAFLD.