Abstract
OBJECTIVES: Clarifying the uncertain causal relationship between periodontitis and infective endocarditis using Mendelian randomization analysis, given their historically perceived association and clinical significance. METHODS: Genetic variation data for acute periodontitis, chronic periodontitis, aggressive periodontitis, and infective endocarditis were obtained from published GWAS in individuals of European ancestry. Instrumental variables significantly associated with periodontitis were selected and univariable Mendelian randomization was conducted to infer the causal association between periodontitis and infective endocarditis. Multivariable Mendelian randomization was also performed to adjust for potential confounders including smoking, drinking, diabetes, and education. RESULTS: Our analysis found no evidence of a causal association between periodontitis and infective endocarditis, with odds ratios (ORs) of 0.992 (95% CI: 0.879-1.120), 0.947 (95% CI: 0.738-1.214), and 1.056 (95% CI: 0.916-1.217) for acute periodontitis, chronic periodontitis, aggressive periodontitis, respectively. The robustness of our findings was confirmed by heterogeneity tests, pleiotropy tests, leave-one-out analyses, and MR-PRESSO. In the multivariable MR analysis, adjusting for smoking, drinking, diabetes, and education, the overall patterns between genetic liability to periodontitis and infective endocarditis remained consistent (all P > .05). CONCLUSION: Our findings indicate that there is no genetic causal association between periodontitis and infective endocarditis.