Assessing Causal Relationships Between Periodontitis and Non-alcoholic Fatty Liver Disease: A Two-Sample Bidirectional Mendelian Randomisation Study.

Abstract

To investigate the causality between periodontitis and non-alcoholic fatty liver disease (NAFLD) using a two-sample bidirectional Mendelian randomisation (MR) analysis. Genetic variations in periodontitis and NAFLD were acquired from genome-wide association studies (GWAS) using the Gene-Lifestyle Interaction in Dental Endpoints, a large-scale meta-analysis, and FinnGen consortia. Data from the first two databases were used to explore the causal relationship between periodontitis and NAFLD ("discovery stage"), and the data from FinnGen was used to validate our results ("validation stage"). We initially performed MR analysis using 5 single nucleotide polymorphisms (SNPs) in the discovery samples and 18 in the replicate samples as genetic instruments for periodontitis to investigate the causative impact of periodontitis on NAFLD. We then conducted a reverse MR analysis using 6 SNPs in the discovery samples and 4 in the replicate samples as genetic instruments for NAFLD to assess the causative impact of NAFLD on periodontitis. We further implemented heterogeneity and sensitivity analyses to assess the reliability of the MR results. Periodontitis was not causally related to NAFLD (odds ratio [OR] = 1.036, 95% CI: 0.914-1.175, p = 0.578 in the discovery stage; OR = 1.070, 95% CI: 0.935-1.224, p = 0.327 in the validation stage), and NAFLD was not causally linked with periodontitis (OR = 1.059, 95% CI: 0.916-1.225, p = 0.439 in the discovery stage; OR = 0.993, 95% CI: 0.896-1.102, p = 0.901 in the validation stage). No heterogeneity was observed among the selected SNPs. Sensitivity analyses demonstrated the absence of pleiotropy and the reliability of our MR results. The present MR analysis showed no genetic evidence for a cause-and-effect relationship between periodontitis and NAFLD. Periodontitis may not directly influence the development of NAFLD and vice versa.