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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2023

Open Access 01-12-2023 | Gastroesophageal Reflux Disease | Research

Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study

Authors: Xiaoxue Cheng, Jiang Shi, Ding Zhang, Caichen Li, Haoxiang Xu, Jianxing He, Wenhua Liang

Published in: BMC Pulmonary Medicine | Issue 1/2023

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Abstract

Background

Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain whether GERD causally influences these diseases. In this study, 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

Our 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 12 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered.

Conclusions

Our study suggested that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, indicating that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases.
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Metadata
Title
Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study
Authors
Xiaoxue Cheng
Jiang Shi
Ding Zhang
Caichen Li
Haoxiang Xu
Jianxing He
Wenhua Liang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2023
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-023-02502-8

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