Assessing Genetic Causality of Periodontal Disease and Atrial Fibrillation by Potential Mediators: A Two-Step Mediating Mendelian Randomization Study

Abstract

Background The independent causality of periodontal disease on atrial fibrillation (AF) and the modifiable risk factors mediating the pathogenesis remain unclear. Method First, to confirm the independent causality, this study underwent the bidirectional and multivariable Mendelian Randomization (MR) underlying the genome-wide association studies (GWAS) of periodontal disease (87497 cases/259234 controls) from the FinnGen and AF (55114 cases/482295 controls) from AFGen. Then, the two-step Mendelian randomization evaluated the mediating role and proportions of 25 candidate factors. Result Periodontal disease was associated with a higher risk of AF with an odds ratio of 1.16 ([95% CI, 1.027–1.314], p = 0.017), independently of dental caries and pulp and periapical disease. Reversely, there is no causation of AF on periodontal disease status. Using the two-step MR, we identified 5 out of 25 candidate mediators as statistically significant; sorted by the mediation proportion, including weight (30.3%), IL-17 (17.2%), TNF (14.08%), coronary atherosclerosis (13.4%) and hypertension (11.6%). Conclusion Our findings preliminarily demonstrated the genetic causality between periodontal disease and atrial fibrillation. For patients suffering from periodontal disease status, it is noted that maintaining oral hygiene, accepting standardized periodontal treatment, and managing body weight are crucial targets for controlling the disease progression towards AF.