Periodontitis and NAFLD-related diseases: A bidirectional two-sample Mendelian randomization study

Background: Epidemiological studies have shown an association between periodontitis and nonalcoholic fatty liver disease (NAFLD)-related diseases. However, a causal relationship between these two diseases remains unclear. To examine the causal relationship between these two diseases, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using genetic markers as proxies.Methods: Statistical summary was obtained from a large genome-wide association study (GWAS) on NAFLD (N = 342,499), nonalcoholic steatohepatitis (NASH, N = 342,499), fibrosis (N = 339,081), cirrhosis (N = 342,499), fibrosis/cirrhosis (N = 334,553), and periodontitis (N = 34,615) in the European ancestry. The inverse variance weighted (IVW) method was used as the main method to estimate the bidirectional association. Sensitivity analysis was performed to evaluate the rigidity of the results.Results: Limited evidence indicated positive causal associations between genetically predicted NAFLD and periodontitis (IVW odds ratio [OR], 1.094; 95% confidence interval [CI], 1.006-1.189; p = 0.036) and between cirrhosis and periodontitis (IVW OR, 1.138; 95% CI, 1.001-1.294; p = 0.048). However, the opposite trend did not indicate a causative effect of periodontitis on NAFLD-related diseases. The sensitivity analysis revealed no obvious pleiotropy or heterogeneity.Conclusions: Our MR analysis provides new evidence in favor of the moderate causal impact of NAFLD on periodontitis. The causal effects of periodontitis on NAFLD-related diseases warrant further investigation.