Correlation between cholelithiasis,cholecystectomy,and gastroesophageal reflux disease
Objective To use mendelian randomization(MR)study to explore the causal relationship between cholelithiasis,cholecystectomy,and gastroesophageal reflux disease(GERD).Methods Based on large-scale genome-wide association studies(GW AS),genetic variants closely associated with cholelithiasis and cholecystectomy were selected as instrumental variables.Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)was used to eliminate outliers.Inverse variance weighting(IVW)was used as the main analysis method and MR-Egger,Weighted median,Simple mode and Weighted mode were used as supplementary analysis methods for causal effect evaluation.Meanwhile,Cochran's Q was used for heterogeneity test.The MR Egger intercept test was used to analyze the level of horizontal pleiotropy,and the leave-one-out method was used to ensure the robustness of the results.Results Inverse variance weighted results showed that cholelithiasis(odds ratio:1.05,95%confidence interval:1.03-1.07,P<0.01)and cholecystectomy(odds ratio:2.56,95%confidence interval:1.76-3.73,P<0.01)were significantly associated with an increased risk of GERD.Cochran's Q test showed that there was heterogeneity in the genetic variants of cholelithiasis(P<0.05),but no significant heterogeneity in the genetic variants of cholecystectomy(P>0.05).MR-Egger intercept analysis did not detect potential horizontal pleiotropy(P>0.05),and the leave-one-out analyses showed that the results were robust.Conclusion Genetically predicted cholelithiasis and cholecystectomy are causally associated with GERD,suggesting that the prevention of GERD should be strengthened in patients with cholelithiasis and after cholecystectomy.