In this study, to provide some basis for the prevention and treatment of NAFLD and lower the incidence and disease burden, TSMR analysis was utilized to analyze the possible causal relationship between leptin and NAFLD from a genetic perspective using GWAS summary statistics for leptin and NAFLD with leptin-related gene polymorphisms as instrumental variables (IVs). The gene discussed is LEP; the disease is metabolic dysfunction-associated steatotic liver disease.