Causal analysis of the association between gastroesophageal reflux disease and idiopathic pulmonary fibrosis

Abstract Background: Recent observational studies have provided evidence of a close association between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF). However, determining the causal relationship between these two conditions remains a challenge. In this study, we employed Mendelian randomization (MR), a genetic method using genome-wide association studies (GWAS), to investigate the causal relationship between GERD and IPF. Methods: In order to evaluate the causality of GERD in IPF, multiple MR methods were employed utilizing the GWAS databases of GERD from 473,524 individuals and of IPF from 451,025. Sensitivity analysis was performed to evaluate the robustness of MR results. Additionally, multi-variant Mendelian randomization (MVMR) was utilized to evaluate potential confounding factors. Results: We found a significant causal relationship between GERD and IPF (odds ratio [OR]: 1.002, 95% confidence interval [CI]: 1.001–1.003, P <0.001). This finding was also supported by the Weighted median analysis (OR: 1.002, 95% CI: 1.002–1.003, P =0.021). The sensitivity analysis did not reveal any significant deviation from the main results. Furthermore, MVMR analysis demonstrated that GERD significantly increased the risk of IPF, even after controlling for possible confounding factors (OR: 1.001, 95% CI: 1.001–1.003, P =0.04). Conclusions: The results of our study provide strong evidence of a causal relationship between GERD and IPF. Based on these findings, it is recommended that interventions be implemented for individuals with GERD to prevent the development of IPF.