Background
Although the association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases was found in previous observational studies, it remains uncertain whether GERD causally influences them. Herein, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases.
Methods
88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings.
Results
This study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25–1.56, P < 0.001), idiopathic pulmonary fibrosis (IPF) (OR 1.43, 95%CI 1.05–1.95, P = 0.022), chronic obstructive disease (COPD) (OR 1.64, 95%CI 1.41–1.93, P < 0.001), chronic bronchitis (OR 1.77, 95%CI 1.15–2.74, P = 0.009), while no correlation was observed for bronchiectasis (OR 0.93, 95%CI 0.68–1.27, P = 0.645). Additionally, GERD was associated with 10 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered.
Conclusions
Our study indicated that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, suggesting that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases.