Common gastrointestinal diseases and chronic obstructive pulmonary disease risk: a bidirectional Mendelian randomization analysis

Abstract

Background: Observational studies suggest an association between gastrointestinal diseases and chronic obstructive pulmonary disease (COPD), but the causal relationship remains unclear. Methods: We conducted bidirectional Mendelian randomization (MR) analysis using summary data from genome-wide association study (GWAS) to explore the causal relationship between common gastrointestinal diseases and COPD. Gastrointestinal diseases included gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), irritable bowel syndrome (IBS), Crohn's disease (CD), ulcerative colitis (UC), functional dyspepsia (FD), non-infectious gastroenteritis (NGE), and constipation (CP). Significant MR analysis results were replicated in the COPD validation cohort. Results: Bidirectional MR analysis supported a bidirectional causal relationship between GERD and COPD, and COPD was also found to increase the risk of IBS and CP. Our study also provided evidence for a bidirectional causal relationship between PUD and COPD, although the strength of evidence may be insufficient. Furthermore, we provided evidence that there is no causal association between CD, UC, FD, NGE, and COPD. Conclusion: This study offers some evidence to clarify the causal relationship between common gastrointestinal diseases and COPD. Further research is needed to understand the underlying mechanisms of these associations.

Keywords: Mendelian randomization; chronic obstructive pulmonary disease; constipation; gastroesophageal reflux disease; gastrointestinal diseases; irritable bowel syndrome; peptic ulcer disease.

FIGURE 1

A is a bidirectional acyclic graph. B is an overview of our study. I: assumption I, II: assumption II; III: assumption III; GERD, gastroesophageal reflux disease; PUD, peptic ulcer disease; IBS, irritable bowel syndrome; CD, Crohn’s disease; UC, ulcerative colitis; FD, functional dyspepsia; NGE, noninfectious gastroenteritis; CP, constipation; COPD, chronic obstructive pulmonary disease; IVW, inverse variance weighting; MR-Egger, MR-Egger regression; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test; MR-RAPS, Mendelian Randomization Robust Adjusted Profile Score.

FIGURE 2

Causal estimate and sensitivity analysis of gastrointestinal diseases as exposure. NSNP, Number of SNPs; OR, odds ratio; 95%LCI, lower limit of 95% confidence interval of OR; 95%UCI, upper limit of 95% confidence interval of OR; p-value, p-value of OR; IVW, inverse variance weighting; MR-Egger, MR-Egger regression; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test; MR-RAPS, Mendelian Randomization Robust Adjusted Profile Score; GERD, gastroesophageal reflux disease; PUD, peptic ulcer disease; IBS, irritable bowel syndrome; CD, Crohn’s disease; UC, ulcerative colitis; FD, functional dyspepsia; NGE, noninfectious gastroenteritis; CP, constipation; COPD, chronic obstructive pulmonary disease.

FIGURE 3

Causal estimate and sensitivity analysis of COPD as exposure. NSNP, Number of SNPs; OR, odds ratio; 95%LCI, lower limit of 95% confidence interval of OR; 95%UCI, upper limit of 95% confidence interval of OR; p-value, p-value of OR; IVW, inverse variance weighting; MR-Egger, MR-Egger regression; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test; MR-RAPS, Mendelian Randomization Robust Adjusted Profile Score; GERD, gastroesophageal reflux disease; PUD, peptic ulcer disease; IBS, irritable bowel syndrome; CD, Crohn’s disease; UC, ulcerative colitis; FD, functional dyspepsia; NGE, noninfectious gastroenteritis; CP, constipation; COPD, chronic obstructive pulmonary disease.