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

作者：Xiaohan Zhang, Chengzhong Lian, Shuqing Shi, Jiaran Li, Lian-Xin Wang, Zezhen Guo, Naixu Liu, Huan Wang, Yuanhui Hu, Bai Du · 发表于：International Dental Journal · 年份：2025 · DOI：10.1016/j.identj.2024.12.029 · 被引用次数：7 · 研究领域：Oral microbiology and periodontitis research、Genetic Associations and Epidemiology、Dental Health and Care Utilization

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 pati...