Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease

Abstract:

Objective Clinical observations and epidemiological investigations have found an association of gastroesophageal reflux disease（GERD） with interstitial lung disease（ILD）. We aimed to investigate whether GERD and ILD are causally associated with each other and the direction of the association through Mendelian randomization（MR） analysis.Methods Eligible single nucleotide poly-morphisms（SNPs）were selected as instrumental variables（IVs） from the pooled data of genome-wide association studies（GWAS）.Two-sample Mendelian randomization analyses were performed using the inverse-variance weighted method（IVW），the MR-Egger regression method，and the weighted median estimator（WME）. The IVW method was used as the main causal analysis. The MR-PRESSO test and MR-Egger regression method were used in sensitivity analysis to detect and correct for horizontal pleiotropy. The leave-one-out method，Cochran’s Q test，and funnel plot were used to assess the stability and reliability of MR results. The odds ratio（OR） was used to evaluate the causality between GERD and ILD.Results The IVW results showed that GERD increased the risk of ILD，and each standard deviation increase in log-transformed GERD resulted in a 22% increase in the risk of ILD（OR=1.22，95%CI=1.11-1.33，P=3.52e-05）. Conversely，ILD also increased the risk of GERD.Conclusion GERD and ILD have a bidirectional causal relationship.