The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation.

Abstract

Introduction and aims: This study aims to examine the possible causal link between periodontal diseases and atrial fibrillation (AF), with a focus on the modifiable risk factors that facilitate this connection.

Method: Firstly, bidirectional and multivariable Mendelian Randomisation (MR) analyses were conducted using genome-wide association studies (GWAS) data on periodontal disease (87,497 cases/259,234 controls) from FinnGen and AF (55,114 cases/482,295 controls) from AFGen. Then, a 2-step MR approach was employed to evaluate the mediating role and proportions of 25 candidate factors among the direct causality between periodontal disease and AF.

Results: Periodontal disease was found to be associated with an increased risk of AF (odds ratio 1.16, 95% CI 1.027-1.314, p = .017), independent of other covariates such as dental caries, pulp, and periapical diseases. Conversely, no causal relationship was detected indicating that AF leads to periodontal disease condition. Furthermore, in the 2-step MR analysis, 5 out of 25 candidate mediators were screened as statistically significant. Ranked by partial mediation proportion, these modifiable mediators included weight (30.3%), IL-17 (17.2%), TNF (14.08%), coronary atherosclerosis (13.4%), and hypertension (11.6%).

Conclusion: Our findings demonstrated the genetic causality between periodontal disease and AF. Maintaining oral hygiene, adopting standardised periodontal therapy, and restricting body weight are critical goals for patients with periodontal disease to mitigate disease progression to AF.