Related Experiment Video
Updated: Jun 7, 2025

Surgical Models of Gastroesophageal Reflux with Mice
Published on: August 25, 2015
Gastroesophageal reflux disease increases predisposition to severe COVID-19: Insights from integrated Mendelian
Jingjing Pan1,2, Jianhua Li1,2
1Department of Microbiology, Zhejiang Provincial Centers for Disease Control and Prevention, Hangzhou, China.
Objective:
This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue-specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized/severe 2019 coronavirus disease (COVID-19).
Methods:
We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD (N = 602,604) and hospitalized COVID-19 (N = 2095,324) as well as severe COVID-19 (N = 1086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD-driven molecular pathway network was constructed using extensive literature data mining to understand the molecular-level impacts of GERD on COVID-19.
Results:
Our results revealed a significant positive genetic correlation between GERD and both hospitalized (rg = 0.418) and severe COVID-19 (rg = 0.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID-19 outcomes, including hospitalized COVID-19 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27-1.44, p = 9.17e - 12) and severe COVID-19 (OR: 1.27, 95% CI: 1.18-1.37, p = 1.20e - 05). Additionally, GERD and both COVID-19 conditions shared one genomic locus with lead-SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome-wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_p = 2.35e - 07) and rs1123573 (eQTL_p = 2.74e - 05). Molecular pathway analysis indicated that GERD might promote the progression of COVID-19 by inducting immune-activated and inflammation-related pathways.
Conclusion:
These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized/severe COVID-19. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID-19.
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...
Single Nucleotide Polymorphisms-SNPs
Esophageal Strictures-I: Introduction
Etiology
The primary cause of esophageal strictures is long-standing gastroesophageal reflux disease (GERD), accounting for about 70 to 80% of adult cases. Chronic acid reflux can lead to injury and scarring of the esophageal lining, culminating in...
Barrett Esophagus-I: Introduction
This constant acid exposure transforms the esophagus's pink mucosal lining (stratified squamous epithelium) into a type of lining more...
Barrett Esophagus-II: Clinical Manifestations and Management
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...

