Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study
IntroductionObservational studies have discovered a contradictory phenomenon between interleukin-17 (IL-17) and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between each subtype of IL-17 and IBD.MethodsWe performed a 2-sample univariable and multivariable mende...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238457/full |
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| author | Yangke Cai Yangke Cai Xuan Jia Liyi Xu Hanwen Chen Siyuan Xie Siyuan Xie Jianting Cai |
| author_facet | Yangke Cai Yangke Cai Xuan Jia Liyi Xu Hanwen Chen Siyuan Xie Siyuan Xie Jianting Cai |
| author_sort | Yangke Cai |
| collection | DOAJ |
| description | IntroductionObservational studies have discovered a contradictory phenomenon between interleukin-17 (IL-17) and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between each subtype of IL-17 and IBD.MethodsWe performed a 2-sample univariable and multivariable mendelian randomization (MR) to determine which subtype of IL-17 is causally related to IBD and its subtypes, and used a series of sensitivity analysis to examine the reliability of the main MR assumptions.ResultsWe found that IL-17B, IL-17E and IL-17RB were significantly associated with an increased risk of UC (IL-17B: OR: 1.26, 95% CI, 1.09-1.46, P < 0.01; IL-17E: OR: 1.17, 95% CI, 1.05-1.30, P < 0.01; IL-17RB: OR: 1.30, 95% CI, 1.20-1.40, P < 0.0001) while IL-17C and IL-17RC showed causal effects on the increased risk of CD (IL-17C: OR: 1.23, 95% CI, 1.21-1.26, P < 0.0001; IL-17RC: OR: 2.01, 95% CI, 1.07-3.75, P=0.03). The results of multivariable MR (MVMR) showed that the causal effects of IL-17B and IL-17E on UC were unilaterally dependent on IL-17RB, while the effects of IL-17C and IL-17RC on CD were interdependent.DiscussionOur study provided new genetic evidence for the causal relationships between each subtype of IL-17 and IBD, promoting future mechanistic research in IBD. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T06:17:22Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-8b5c04c953fc4d4dbfc41de295441f482023-11-17T12:11:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12384571238457Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization studyYangke Cai0Yangke Cai1Xuan Jia2Liyi Xu3Hanwen Chen4Siyuan Xie5Siyuan Xie6Jianting Cai7Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaZhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaZhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaIntroductionObservational studies have discovered a contradictory phenomenon between interleukin-17 (IL-17) and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between each subtype of IL-17 and IBD.MethodsWe performed a 2-sample univariable and multivariable mendelian randomization (MR) to determine which subtype of IL-17 is causally related to IBD and its subtypes, and used a series of sensitivity analysis to examine the reliability of the main MR assumptions.ResultsWe found that IL-17B, IL-17E and IL-17RB were significantly associated with an increased risk of UC (IL-17B: OR: 1.26, 95% CI, 1.09-1.46, P < 0.01; IL-17E: OR: 1.17, 95% CI, 1.05-1.30, P < 0.01; IL-17RB: OR: 1.30, 95% CI, 1.20-1.40, P < 0.0001) while IL-17C and IL-17RC showed causal effects on the increased risk of CD (IL-17C: OR: 1.23, 95% CI, 1.21-1.26, P < 0.0001; IL-17RC: OR: 2.01, 95% CI, 1.07-3.75, P=0.03). The results of multivariable MR (MVMR) showed that the causal effects of IL-17B and IL-17E on UC were unilaterally dependent on IL-17RB, while the effects of IL-17C and IL-17RC on CD were interdependent.DiscussionOur study provided new genetic evidence for the causal relationships between each subtype of IL-17 and IBD, promoting future mechanistic research in IBD.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238457/fullinflammatory bowel diseaseinterleukin-17Mendelian randomizationmultivariable Mendelian randomizationgenetic epidemiology |
| spellingShingle | Yangke Cai Yangke Cai Xuan Jia Liyi Xu Hanwen Chen Siyuan Xie Siyuan Xie Jianting Cai Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study Frontiers in Immunology inflammatory bowel disease interleukin-17 Mendelian randomization multivariable Mendelian randomization genetic epidemiology |
| title | Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study |
| title_full | Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study |
| title_fullStr | Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study |
| title_full_unstemmed | Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study |
| title_short | Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study |
| title_sort | interleukin 17 and inflammatory bowel disease a 2 sample mendelian randomization study |
| topic | inflammatory bowel disease interleukin-17 Mendelian randomization multivariable Mendelian randomization genetic epidemiology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238457/full |
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