Genetic evidence causally linking gastroesophageal reflux disease to cholecystitis：A two- sample Mendelian randomization study

Abstract

Abstract Background and aims: Overlapping symptoms of gastroesophageal reflux disease (GERD) and cholecystitis include belching, acid reflux, and heartburn. Nevertheless, the causal relationship between these two conditions remains uncertain. The study aimed to investigate the causal relationship between GERD and cholecystitis via the Mendelian randomization (MR) approach.Methods A two-sample MR analysis utilizing the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods was conducted to assess the causal effects of GERD on the risk of cholecystitis. The genome-wide association studies (GWASs) for GERD (n = 602604) and cholecystitis (n = 361194) were obtained from the MR-base platform. The pleiotropy and heterogeneity were assessed using various techniques.Results A total of 77 single nucleotide polymorphisms from GWASs with GERD were selected as instrumental variables (IVs). The primary IVW method demonstrated a significant association between GERD and an elevated risk of cholecystitis [odds ratio (OR) = 1.004; 95% CI 1.003–1.005, p = 2.68×10− 9]. The absence of heterogeneity and pleiotropy in the data suggested that the results were dependable.Conclusion Our study demonstrated a positive correlation between GERD and the likelihood of developing cholecystitis. These findings may serve as a fundamental basis for comprehending the intricate interplay between GERD and cholecystitis. However, additional investigations are warranted to elucidate the precise underlying mechanisms of this plausible causal relationship.