Related Experiment Video
Updated: May 20, 2025

Surgical Models of Gastroesophageal Reflux with Mice
Published on: August 25, 2015
Observational, causal relationship and shared genetic basis between cholelithiasis and gastroesophageal reflux
Yanlin Lyu1,2,3, Shuangshuang Tong1,3, Wentao Huang1,2
1Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
Objective:
Cholelithiasis and gastroesophageal reflux disease (GERD) contribute to significant health concerns. We aimed to investigate the potential observational, causal, and genetic relationships between cholelithiasis and GERD.
Design:
The observational correlations were assessed based on the prospective cohort study from UK Biobank. Then, by leveraging the genome-wide summary statistics of cholelithiasis (N = 334,277) and GERD (N = 332,601), the bidirectional causal associations were evaluated using Mendelian randomization (MR) analysis. Subsequently, a series of genetic analyses was used to assess the genetic correlation, shared loci, and genes between cholelithiasis and GERD.
Results:
The prospective cohort analyses revealed a significantly increased risk of GERD in individuals with cholelithiasis (hazard ratio [HR] = 1.99; 95% confidence interval [CI], 1.89-2.10) and a higher risk of cholelithiasis among patients with GERD (HR = 2.30; 95% CI, 2.18-2.44). The MR study indicated the causal effect of genetic liability to cholelithiasis on the incidence of GERD (odds ratio [OR] = 1.08; 95% CI, 1.05-1.11) and the causal effect of genetic predicted GERD on cholelithiasis (OR = 1.15; 95% CI, 1.02-1.31). In addition, cholelithiasis and GERD exhibited a strong genetic association. Cross-trait meta-analyses identified 5 novel independent loci shared between cholelithiasis and GERD. Three shared genes, including SUN2, CBY1, and JOSD1, were further identified as novel risk genes.
Conclusion:
The elucidation of the shared genetic basis underlying the phenotypic relationship of these 2 complex phenotypes offers new insights into the intrinsic linkage between cholelithiasis and GERD, providing a novel research direction for future therapeutic strategy and risk prediction.
Related Concept Videos
Gastroesophageal Reflux Disease I: Meaning and Pathophysiology
Gastroesophageal Reflux Disease II: Clinical Features and Management
Clinical Manifestations
GERD presents itself in a multitude of ways, with symptoms varying from person to person. The hallmark symptoms are...
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Peptic Ulcer Disease I: Introduction
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
Pathophysiology of Peptic Ulcer Disease: Injurious Factors
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
Barrett Esophagus-I: Introduction
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...

