The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation
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 we...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | International Dental Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0020653925000036 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850143571611484160 |
|---|---|
| author | Xiaohan Zhang Chengzhong Lian Shuqing Shi Jiaran Li Lianxin Wang Zezhen Guo Naixu Liu Huan Wang Yuanhui Hu Bai Du |
| author_facet | Xiaohan Zhang Chengzhong Lian Shuqing Shi Jiaran Li Lianxin Wang Zezhen Guo Naixu Liu Huan Wang Yuanhui Hu Bai Du |
| author_sort | Xiaohan Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-45f2228ba3c74d6f98e1eb2c571e3cc8 |
| institution | OA Journals |
| issn | 0020-6539 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Dental Journal |
| spelling | doaj-art-45f2228ba3c74d6f98e1eb2c571e3cc82025-08-20T02:28:40ZengElsevierInternational Dental Journal0020-65392025-06-017532093210310.1016/j.identj.2024.12.029The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial FibrillationXiaohan Zhang0Chengzhong Lian1Shuqing Shi2Jiaran Li3Lianxin Wang4Zezhen Guo5Naixu Liu6Huan Wang7Yuanhui Hu8Bai Du9Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Oral Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, ChinaDepartment of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, ChinaFaculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, AustraliaDepartment of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaCorresponding author. Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixiange, Xicheng District, Beijing 100053, China; Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaCorresponding author. Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixiange, Xicheng District, Beijing 100053, China; Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaIntroduction 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.http://www.sciencedirect.com/science/article/pii/S0020653925000036Periodontal disease1Atrial fibrillation2Cytokines3Mendelian randomisation4Mediating pathway5 |
| spellingShingle | Xiaohan Zhang Chengzhong Lian Shuqing Shi Jiaran Li Lianxin Wang Zezhen Guo Naixu Liu Huan Wang Yuanhui Hu Bai Du The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation International Dental Journal Periodontal disease1 Atrial fibrillation2 Cytokines3 Mendelian randomisation4 Mediating pathway5 |
| title | The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation |
| title_full | The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation |
| title_fullStr | The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation |
| title_full_unstemmed | The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation |
| title_short | The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation |
| title_sort | 2 step mendelian randomisation study assesses genetic causality and potential mediators of periodontal disease and atrial fibrillation |
| topic | Periodontal disease1 Atrial fibrillation2 Cytokines3 Mendelian randomisation4 Mediating pathway5 |
| url | http://www.sciencedirect.com/science/article/pii/S0020653925000036 |
| work_keys_str_mv | AT xiaohanzhang the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT chengzhonglian the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT shuqingshi the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT jiaranli the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT lianxinwang the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT zezhenguo the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT naixuliu the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT huanwang the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT yuanhuihu the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT baidu the2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT xiaohanzhang 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT chengzhonglian 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT shuqingshi 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT jiaranli 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT lianxinwang 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT zezhenguo 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT naixuliu 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT huanwang 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT yuanhuihu 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation AT baidu 2stepmendelianrandomisationstudyassessesgeneticcausalityandpotentialmediatorsofperiodontaldiseaseandatrialfibrillation |