| Title: | Observational, causal relationship and shared genetic basis between cholelithiasis and gastroesophageal reflux disease: evidence from a cohort study and comprehensive genetic analysis |
| Journal: | GigaScience |
| Published: | 6 Jan 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40139907/ |
| DOI: | https://doi.org/10.1093/gigascience/giaf023 |
| URL: | http://dx.doi.org/10.1093/gigascience/giaf023 |
Publication 14870
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Abstract
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.</p>
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.</p>
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.</p>
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.</p>
14 Keywords
- Aged
- Cholelithiasis
- Cohort Studies
- Female
- Gastroesophageal Reflux
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Factors
11 Authors
- Yanlin Lyu
- Shuangshuang Tong
- Wentao Huang
- Yuying Ma
- Ruijie Zeng
- Rui Jiang
- Ruibang Luo
- Felix W Leung
- Qizhou Lian
- Weihong Sha
- Hao Chen
1 Application
| Application ID | Title |
|---|---|
| 83339 | Characterization of risk factors and biomarkers for digestive tract diseases |
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