A bidirectional Mendelian randomization study integrating genome-wide association studies, expression quantitative trait locus, and methylation quantitative trait locus data revealed causal relationship between heavy cigarette dependence and Barrett’s esophagus
Background: The association between smoking dependence and the risk of developing Barrett’s esophagus remains unclear. This study aimed to investigate whether a causal relationship exists between smoking dependence and Barrett’s esophagus, using Mendelian randomization analysis. Methods: Two-sample...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-02-01
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| Series: | SAGE Open Medicine |
| Online Access: | https://doi.org/10.1177/20503121251316595 |
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| Summary: | Background: The association between smoking dependence and the risk of developing Barrett’s esophagus remains unclear. This study aimed to investigate whether a causal relationship exists between smoking dependence and Barrett’s esophagus, using Mendelian randomization analysis. Methods: Two-sample Mendelian randomization analysis was conducted to evaluate the impact of smoking and Barrett’s esophagus. Additionally, we applied summary data-based Mendelian randomization techniques to combine information from genome-wide association studies (GWAS) with expression quantitative trait locus and methylation quantitative trait locus. Results: Multivariable Mendelian randomization showed an association between smoking per day (odds ratio = 1.2, 95% confidence interval: 1.038–1.38, p = 0.014) or current smoking (odds ratio = 2.41, 95% confidence interval: 1.06–5.5, p = 0.037) and Barrett’s esophagus. Inverse variance-weighted methods of bidirectional Mendelian randomization also revealed that smoking per day was significantly associated with elevated risks of Barrett’s esophagus (odds ratio = 1.34, 95% confidence interval: 1.092–1.649, p = 0.005), while Barrett’s esophagus was also a susceptibility factor for smoking per day (odds ratio = 1.05, 95% confidence interval: 1.017–1.087, p = 0.003). By incorporating consistent summary data-based Mendelian randomization associations between DNA methylation and smoke/Barrett’s esophagus, gene expression and smoke/Barrett’s esophagus, and DNA methylation and gene expression, we identified that the genetic variant-cg00935895-RBM43 (ENSG00000184898)-smoke/Barrett’s esophagus axis exerted an effect on smoke/Barrett’s esophagus by altering the DNA methylation level, which regulated the expression level of RBM43. Conclusions: Our study provides evidence of a bidirectional causal association between smoking and Barrett’s esophagus from a genetic perspective, which sheds new light on the potential role of RBM43 as a mediator in facilitating the impact of smoking and Barrett’s esophagus. |
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| ISSN: | 2050-3121 |