Causal association between periodontitis and hepatobiliary diseases: genetic insights from Mendelian randomization
10.12016/j.issn.2096-1456.202550127
- Author:
ZHAO Li
1
;
CHEN Shaopeng
2
;
CHEN Zhen
2
;
CHEN Yueqi
2
;
YU Ting
2
Author Information
1. Hospital of Stomatology, Sun Yat-sen University & Guangdong Provincial Key Laboratory of Stomatology
2. Department of Periodontology, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University
- Publication Type:Journal Article
- Keywords:
Periodontal diseases;
hepatobiliary diseases;
nonalcoholic fatty liver disease;
cirrhosis;
liver cancer;
cholelithiasis;
acalculous cholecystitis;
Mendelian randomization
- From:
Journal of Prevention and Treatment for Stomatological Diseases
2025;33(10):873-883
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the reciprocal causal relationships between periodontitis and hepatobiliary diseases through Mendelian randomization (MR) analyses, to provide evidence for joint prevention and clinical decision-making in patients with concurrent periodontitis and hepatobiliary diseases.
Methods:Single nucleotide polymorphisms (SNPs) were extracted from the largest genome-wide association study on periodontitis (17 353 cases, 28 210 controls) and hepatobiliary diseases within the European ancestry and used as instrumental variables (IVs). The strength of the associations was examined by calculating the F-statistic. The SNPs significantly associated with the outcome were removed by scanning on Phenoscanner platform. Bidirectional causal associations between periodontitis and hepatobiliary diseases were estimated using inverse variance weighted (IVW), MR-Egger, and Weighted Median methods. The robustness of the findings was further verified through additional sensitive MR approaches, including Cochran’s Q statistic （IVW）, Rucker’s Q statistic （MR-Egger）, MR-PRESSO and Leave-one-out analysis. Further MR analyses, utilizing other available genome-wide association studies (GWAS) on hepatobiliary diseases, were conducted to validate the results.
Results:The IVW method found that periodontitis had a causal impact on acalculous cholecystitis (odds ratio = 1.277, 95% CI 1.097-1.485, P=0.002), implying an increased risk of acalculous cholecystitis associated with periodontitis, while the MR-Egger regression and Weighted Median failed to observe significant causal effects of periodontitis on acalculous cholecystitis. However, no bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer were observed using IVW, MR-Egger regression and Weighted Median. The bidirectional causal relationships were deemed unlikely to be influenced by horizontal pleiotropy. Further, the validation analysis based on alternative GWAS data suggested parallel results.
Conclusions:The MR analyses suggest that periodontitis may elevate the risk of acalculous cholecystitis. Further investigations, including clinical studies and mechanistic explorations, are warranted to validate these findings. However, the MR analyses do not support bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer.
- Full text:2025101010371223867牙周炎与肝胆疾病的因果关联：一项双向孟德尔随机化分析.pdf
