Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-023-02502-8 |
| _version_ | 1797784748655902720 |
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| author | Xiaoxue Cheng Jiang Shi Ding Zhang Caichen Li Haoxiang Xu Jianxing He Wenhua Liang |
| author_facet | Xiaoxue Cheng Jiang Shi Ding Zhang Caichen Li Haoxiang Xu Jianxing He Wenhua Liang |
| author_sort | Xiaoxue Cheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T00:44:19Z |
| format | Article |
| id | doaj.art-3704721b057c4f409c9ce73b43fa7738 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-03-13T00:44:19Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-3704721b057c4f409c9ce73b43fa77382023-07-09T11:05:09ZengBMCBMC Pulmonary Medicine1471-24662023-07-0123111110.1186/s12890-023-02502-8Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization studyXiaoxue Cheng0Jiang Shi1Ding Zhang2Caichen Li3Haoxiang Xu4Jianxing He5Wenhua Liang6Nanshan School, Guangzhou Medical UniversityDepartment of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Gastroenterology, Maoming Hospital of Guangzhou University of Chinese MedicineDepartment of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical UniversityThe Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine) of Guangzhou University of Chinese MedicineDepartment of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical UniversityAbstract 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.https://doi.org/10.1186/s12890-023-02502-8Gastroesophageal reflux diseaseChronic respiratory diseasesMendelian randomizationGeneticCausality |
| spellingShingle | Xiaoxue Cheng Jiang Shi Ding Zhang Caichen Li Haoxiang Xu Jianxing He Wenhua Liang Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study BMC Pulmonary Medicine Gastroesophageal reflux disease Chronic respiratory diseases Mendelian randomization Genetic Causality |
| title | Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study |
| title_full | Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study |
| title_fullStr | Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study |
| title_full_unstemmed | Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study |
| title_short | Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: a mendelian randomization study |
| title_sort | assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases a mendelian randomization study |
| topic | Gastroesophageal reflux disease Chronic respiratory diseases Mendelian randomization Genetic Causality |
| url | https://doi.org/10.1186/s12890-023-02502-8 |
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