Oral health status and esophageal diseases: Univariate and multivariate Mendelian randomization analyses

Emerging evidence suggests a profound connection between oral health status and esophageal diseases. Nevertheless, the causal relationship remains controversial. This Mendelian randomization (MR) study was performed to probe into the genetic causality between oral health status and esophageal diseases. Summary statistics from genome-wide association studies were obtained from the FinnGen project and the UK Biobank consortium. The number of instrumental single nucleotide polymorphisms per trait ranged from approximately 8.97 million to 16.38 million. The analyzed datasets included sample sizes of up to 4,63,010 individuals. Univariable MR analyses were conducted to explore the potential bidirectional causality between oral health status and esophageal diseases. Inverse-variance weighted method was primarily employed. To confirm the reliability of our findings, we conducted sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and leave-one-out test. Furthermore, we conducted multivariable MR analysis to adjust for potential confounders. Mouth ulcers were strongly associated with esophageal carcinoma and Barrett's esophagus. Toothache tended to increase the risk of Barrett's esophagus. Excessive attrition of teeth was an increased risk for gastro-esophageal reflux. Patients with dental caries exhibited an increased susceptibility to ulcer of esophagus. In reverse, Barrett's esophagus increased the risk of chronic periodontitis and excessive attrition of teeth. Ulcer of esophagus tended to increase the risk of excessive attrition of teeth. Sensitivity analysis yielded consistent results, indicating no heterogeneity or pleiotropy. This study suggests potential causal associations between oral health status and esophageal diseases.