The Causal Relationship Between Gastroesophageal Reflux Disease and Chronic Obstructive Pulmonary Disease: A Bidirectional Two-Sample Mendelian Randomization Study

Background: Gastroesophageal reflux disease (GERD) and Chronic Obstructive Pulmonary Disease (COPD) often coexist and have been associated in observational studies. However, the real potential causal relationship between GERD and COPD is unknown and not well established.Methods: In this study, we conducted a bidirectional two-sample Mendelian randomization(MR) to estimate whether GERD and COPD are causal. The GERD genetic data is from summary level data of a genome-wide association (GWAS) meta-analysis (Ncases = 71,522, Ncontrol=26,079). The COPD GWAS are available from the FinnGen (Ncases=16,410, Ncontrol=283,589). MR-Egger regression, Weighted Median, and Inverse-variance weighted (IVW) were used for MR analysis from the R package "TwoSampleMR", and IVW was the dominant estimation method. Additionally, the MR pleiotropy residual sum and outlier (MR-PRESSO), Cochran Q statistic, and leave-one-out analysis were used to detect and correct for the effect of heterogeneity and horizontal pleiotropy.Results: MR analysis indicated that GERD was causally associated with an increased risk of COPD (IVW odds ratio (OR): 1.3760, 95% confidence interval (CI): 1.1565-1.6371, P=0.0003), and vice versa (IVW OR: 1.1728, 95% CI:1.0613-1.2961, P=0.0018). The analyses did not reveal any pleiotropy or heterogeneity.Conclusion: Our study revealed possible evidence for a bidirectional causal relationship between GERD and COPD. Implementing screening and preventive strategies for GERD in individuals with COPD, and vice versa, will be crucial in future healthcare management. Further studies are needed to elucidate the mechanisms underlying the causal relationship between GERD and COPD.