Causal relationship between gastroesophageal reflux disease and chronic obstructive respiratory disease: a bidirectional Mendelian randomization study

Numerous observational studies have posited that gastroesophageal reflux disease (GERD) might amplify the risk of chronic airway conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Yet, a definitive causal link remains to be established. To this end, we utilized a two-sample Mendelian randomization approach (MR) to investigate the potential causal dynamics between GERD and these chronic obstructive respiratory diseases. Using a two-sample bidirectional MR, we explored the causal influence of GERD on the risks of developing COPD and asthma, drawing on aggregated genome-wide association study data from European cohorts. Our analysis elucidated a notable causal relationship, with individuals genetically inclined towards GERD exhibiting a significantly elevated propensity to develop COPD (odds ratio [OR] = 1.520, 95% confidence interval [CI] 1.376−1.680, P = 2.173×10-16) and asthma (OR = 1.420, 95% CI 1.340−1.504, P = 1.269×10-32). The absence of heterogeneity and pleiotropy was confirmed through the Cochran Q test, funnel plots, MR-Egger intercept test, and MR-PRESSO. Directional causality was further substantiated by Steiger testing. Conversely, reverse MR analyses did not identify a significant causal pathway between COPD or asthma and GERD onset. This investigation substantiates a robust positive correlation between GERD and increased risks for COPD and asthma, laying a foundational basis for incorporating GERD management into preventive and therapeutic strategies for these chronic obstructive respiratory diseases.