Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: A Mendelian randomization study

Abstract

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.

Gastroesophageal Reflux and Chronic Rhinosinusitis: A Mendelian Randomization Study

“…Evidence from prior two-sample MR studies suggests that GERD causally influences asthma 19 , and asthma elevates the risk of CRS 18 . In light of these findings, our study conducted a network MR analysis to investigate whether asthma serves as a mediator in the relationship between GERD and CRS.…”

“…Additionally, we used multivariable MR to explore the direct influence of GERD on CRS. Considering GERD's proven causal effect on asthma 19 , network MR analysis was performed to explore the potential mediating role of asthma between GERD and CRS. These analyses could offer fresh insights into CRS prevention by elucidating GERD's causal role in CRS development.…”