A large genetic study reported that genetic liability to gastroesophageal reflux disease was causally associated, via Mendelian randomization, with increased risk of several ear and balance disorders, including Ménière’s disease, sensorineural hearing loss, vestibular dysfunction, and tinnitus. Barrett’s esophagus showed no association with any of the outcomes.
Gastroesophageal reflux disease (GERD) liability was linked to higher odds of Ménière’s disease, sensorineural hearing loss, and vestibular dysfunction. Associations were also observed with constant, frequent, and occasional tinnitus, though the absolute effect sizes were small (odds ratios ranging from 1.006 to 1.019). No relationship was found with chronic suppurative otitis media. In contrast, Barrett’s esophagus showed no associations across Ménière’s disease, sensorineural hearing loss, vestibular dysfunction, or tinnitus.
“This causal relationship reveals the extensive pathological impact of GERD — reflux substances not only damage the proximal esophagus, throat, and airways, but their effects may indirectly affect the middle ear and inner ear through the eustachian tube or systemic inflammatory responses,” said Wen Zhao, of the School of Graduate, Hebei Chinese Medical University, and colleagues.
Researchers used a two-sample Mendelian randomization design with genome-wide association study data from European ancestry cohorts. The GERD data set included more than 600,000 participants, and the Barrett’s esophagus data set included more than 56,000. Ear disorder outcomes were drawn from UK Biobank and FinnGen data sets. The inverse-variance–weighted method was the primary analytic approach, with additional methods applied for robustness. Genetic instruments were selected to minimize weak instrument bias.
Sensitivity analyses showed no evidence of pleiotropy and stable leave-one-out results. Most outcomes were consistent, though some tinnitus models showed small signals of heterogeneity.
Limitations included restriction to European ancestry populations, which may limit generalizability. The Barrett’s esophagus data set was smaller, potentially reducing power to detect associations. Diagnostic misclassification across data sets was possible, and overlap in genetic risk between GERD and Barrett’s esophagus complicated interpretation.
The researchers concluded that genetic liability to GERD increased the risk of Ménière’s disease, sensorineural hearing loss, vestibular dysfunction, and tinnitus, though the effect sizes for tinnitus were small. Barrett’s esophagus was not causally linked to any ear or balance disorder.
The authors reported no conflicts of interest.
