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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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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| author | Zhou An Meichun Zeng Xianhua Wang |
| author_facet | Zhou An Meichun Zeng Xianhua Wang |
| author_sort | Zhou An |
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| description | 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. |
| format | Article |
| id | doaj-art-c6c948c2278a41eeaadd6747a6ea7e4e |
| institution | Kabale University |
| issn | 2050-3121 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SAGE Publishing |
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| series | SAGE Open Medicine |
| spelling | doaj-art-c6c948c2278a41eeaadd6747a6ea7e4e2025-02-08T07:03:58ZengSAGE PublishingSAGE Open Medicine2050-31212025-02-011310.1177/20503121251316595A 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 esophagusZhou An0Meichun Zeng1Xianhua Wang2Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Endoscope, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, ChinaBackground: 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.https://doi.org/10.1177/20503121251316595 |
| spellingShingle | Zhou An Meichun Zeng Xianhua Wang 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 SAGE Open Medicine |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1177/20503121251316595 |
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