Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study
Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.992080/full |
| _version_ | 1797959934684430336 |
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| author | Yi Liu Yi Liu Zhihan Xiao Kun Ye Kun Ye Linlin Xu Yanping Zhang |
| author_facet | Yi Liu Yi Liu Zhihan Xiao Kun Ye Kun Ye Linlin Xu Yanping Zhang |
| author_sort | Yi Liu |
| collection | DOAJ |
| description | Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD.Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran’s Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs).Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods.Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU. |
| first_indexed | 2024-04-11T00:39:38Z |
| format | Article |
| id | doaj.art-cca862daed02429a857c8ef0700e15dc |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T00:39:38Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-cca862daed02429a857c8ef0700e15dc2023-01-06T12:47:00ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.992080992080Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization studyYi Liu0Yi Liu1Zhihan Xiao2Kun Ye3Kun Ye4Linlin Xu5Yanping Zhang6Department of Digestive System, Anqing Municipal Hospital, Anqing, ChinaDepartment of Digestive System, Wannan Medical College, Wuhu, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Digestive System, Anqing Municipal Hospital, Anqing, ChinaDepartment of Digestive System, Wannan Medical College, Wuhu, ChinaDepartment of Digestive System, Anqing Municipal Hospital, Anqing, ChinaDepartment of Digestive System, Anqing Municipal Hospital, Anqing, ChinaBackground: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD.Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran’s Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs).Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods.Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU.https://www.frontiersin.org/articles/10.3389/fgene.2022.992080/fullsmokingalcohol consumptiondiabetesbody mass indexpeptic ulcerMendelian randomization |
| spellingShingle | Yi Liu Yi Liu Zhihan Xiao Kun Ye Kun Ye Linlin Xu Yanping Zhang Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study Frontiers in Genetics smoking alcohol consumption diabetes body mass index peptic ulcer Mendelian randomization |
| title | Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study |
| title_full | Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study |
| title_fullStr | Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study |
| title_full_unstemmed | Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study |
| title_short | Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study |
| title_sort | smoking alcohol consumption diabetes body mass index and peptic ulcer risk a two sample mendelian randomization study |
| topic | smoking alcohol consumption diabetes body mass index peptic ulcer Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.992080/full |
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