Association Between Gastroesophageal Reflux Disease, Barrett’s Esophagus and Ear Disorders: A Mendelian Randomization Study

Wen Zhao,1,* Xu-Rui Hao,1,* Han-Lin Zhao,1 Ye-Sen Ma,1 Han-Xu Li,1 Qian Yang,1– 3 Jian-Ming Jiang,1,2,4 Hai-Yan Bai1– 3 1School of Graduate, Hebei Chinese Medical University, Shijiazhuang, People’s Republic of China; 2Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, Shijiazhuang, People’s Republic of China; 3Key Laboratory of Hebei Province Turbidity Toxin Syndrome, Shijiazhuang, People’s Republic of China; 4Hebei Medical University, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Yan Bai, Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, No. 389, Zhongshan Road, Shijiazhuang, Hebei, 050011, People’s Republic of China, Tel +8613780306076, Email [email protected] Jian-Ming Jiang, Department of Gastroenterology, Hebei Provincial Hospital of Chinese Medicine, No. 389, Zhongshan Road, Shijiazhuang, Hebei, 050011, People’s Republic of China, Tel +8613831173221, Email [email protected]: This study aims to examine the correlation between gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and ear disorders using Mendelian randomization (MR).Methods: For GERD, BE, and ear disorders, GWAS genetic data from individuals of European ancestry in the IEU GWAS database (https://gwas.mrcieu.ac.uk/) was utilized in this study. Three MR methods were applied for preliminary analysis, with causal estimates determined using the inverse variance weighted method. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Results: Potential effects of genetically predicted GERD on ear disorders were identified in this study. GERD was associated with Ménière’s disease (OR = 1.334, 95% CI: 1.073– 1.671, p = 0.009), sensorineural hearing loss (OR = 1.127, 95% CI: 1.019– 1.245, p = 0.019), vestibular dysfunction (OR = 1.178, 95% CI: 1.025– 1.354, p = 0.021), constant tinnitus (OR = 1.019, 95% CI: 1.009– 1.029, p = 0.0003), tinnitus occurring most of the time (OR = 1.007, 95% CI: 1.001– 1.012, p = 0.019), and occasional tinnitus (OR = 1.014, 95% CI: 1.005– 1.023, p = 0.002). Higher GERD levels were linked to an increased risk of these ear disorders. For individuals who never experienced tinnitus (OR = 0.939, 95% CI: 0.923– 0.957, p = 1.2721E-11), elevated GERD levels were associated with a reduced likelihood of never experiencing tinnitus. No causal association was found between GERD and otitis media (OR = 1.093, 95% CI: 0.884– 1.352, p = 0.412). BE demonstrated no causal relationship with ear disorder risk.Conclusion: Under MR assumptions, the findings of this study indicate that GERD may increase the risk of tinnitus, Ménière’s disease, vestibular dysfunction, and sensorineural hearing loss.Keywords: Barrett’s esophagus, gastroesophageal reflux disease, Mendelian randomization, ear disorders, Ménière’s disease