Gastroesophageal reflux disease and the risk of respiratory diseases: a Mendelian randomization study.

Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2003-

Respiratory Tract Diseases* ; Lung Neoplasms* ; Bronchitis* ; Gastroesophageal Reflux*/complications ; Gastroesophageal Reflux*/genetics ; Pulmonary Embolism* ; Pneumonia* ; Pulmonary Disease, Chronic Obstructive*/genetics; Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis

Background: Observational studies have suggested a suspected association between gastroesophageal reflux disease (GERD) and respiratory diseases, but the causality remains equivocal. The goal of this study was to evaluate the causal role of GERD in respiratory diseases by employing Mendelian randomization (MR) studies.
Methods: We conducted Mendelian randomization analysis based on summary data of genome-wide association studies (GWASs) and three MR statistical techniques (inverse variance weighted, weighted median and MR-Egger) were employed to assess the probable causal relationship between GERD and the risk of respiratory diseases. Sensitivity analysis was also carried out to ensure more trustworthy results, which involves examining the heterogeneity, pleiotropy and leave-one-SNP-out method. We also identified 33 relevant genes and explored their distribution in 26 normal tissues.
Results: In the analysis, for every unit increase in developing GERD, the odds ratio for developing COPD, bronchitis, pneumonia, lung cancer and pulmonary embolism rose by 72% (OR IVW  = 1.72, 95% CI 1.50; 1.99), 19% (OR IVW  = 1.19, 95% CI 1.11; 1.28), 16% (OR IVW  = 1.16, 95% CI 1.07; 1.26), 0. 3% (OR IVW  = 1.003, 95% CI 1.0012; 1.0043) and 33% (OR IVW  = 1.33, 95% CI 1.12; 1.58), respectively, in comparison with non-GERD cases. In addition, neither heterogeneity nor pleiotropy was found in the study. This study also found that gene expression was higher in the central nervous system and brain tissue than in other normal tissues.
Conclusions: This study provided evidence that people who developed GERD had a higher risk of developing COPD, bronchitis, pneumonia, lung cancer and pulmonary embolism. Our research suggests physicians to give effective treatments for GERD on respiratory diseases. By exploring the gene expression, our study may also help to reveal the role played by the central nervous system and brain tissue in developing respiratory diseases caused by GERD.
(© 2024. The Author(s).)

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Keywords: Gastroesophageal reflux disease; Genome-wide association studies; Mendelian randomization (MR); Respiratory diseases

Date Created: 20240116 Date Completed: 20240118 Latest Revision: 20240627

20240627

PMC10790464

10.1186/s12967-023-04786-0

38229096