Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis
BackgroundObservational studies suggest an association between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn’s disease (CD)] and Primary sclerosing cholangitis (PSC), but the causal association between the two diseases remains unclear.MethodsWe used two-sample Mendeli...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.649376/full |
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| author | Ying Xie Xuejie Chen Minzi Deng Yuhao Sun Xiaoyan Wang Jie Chen Changzheng Yuan Therese Hesketh Therese Hesketh |
| author_facet | Ying Xie Xuejie Chen Minzi Deng Yuhao Sun Xiaoyan Wang Jie Chen Changzheng Yuan Therese Hesketh Therese Hesketh |
| author_sort | Ying Xie |
| collection | DOAJ |
| description | BackgroundObservational studies suggest an association between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn’s disease (CD)] and Primary sclerosing cholangitis (PSC), but the causal association between the two diseases remains unclear.MethodsWe used two-sample Mendelian randomization (MR) to estimate the causal association between IBD and PSC. We chose single nucleotide polymorphisms (SNPs) data for analysis, obtained from previous genome-wide association studies (GWASs). Pleiotropy, heterogeneity, and sensitivity analyses were performed for quality control.ResultsWe found that the causal associations between IBD (both UC and CD) and PSC were significant (e.g., IBD and PSC, Robust adjusted profile score (RAPS) OR = 1.29, 95% CI 1.16∼1.44, p< 0.01; UC and PSC, RAPS OR = 1.40, 95% CI 1.23∼1.58, p< 0.01; CD and PSC, RAPS OR = 1.13, 95% CI 1.02∼1.26, p = 0.02). MR Egger, IVW, and ML tests found statistical heterogeneity between determined IV estimates. The leave-one-out analysis also indicated the sensitivity of the SNPs (e.g., IBD and PSC, MR-Egger Q = 644.30, p< 0.01; UC and PSC, MR-Egger Q = 378.30, p< 0.01; UC and PSC, MR-Egger Q = 538.50, p < 0.01).ConclusionMR analyses support the positive causal effect of IBD (including UC and CD) on PSC in a European population. We provide suggestions for preventing and treating the two diseases. |
| first_indexed | 2024-12-16T18:40:23Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T18:40:23Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-196d64a2b4b24d658111ff352cc1c80c2022-12-21T22:21:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-03-011210.3389/fgene.2021.649376649376Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization AnalysisYing Xie0Xuejie Chen1Minzi Deng2Yuhao Sun3Xiaoyan Wang4Jie Chen5Changzheng Yuan6Therese Hesketh7Therese Hesketh8Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, ChinaCentre for Global Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, ChinaCentre for Global Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Big Data and Health Science, Zhejiang University School of Medicine, Hangzhou, ChinaCentre for Global Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute for Global Health, University College London, London, United KingdomBackgroundObservational studies suggest an association between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn’s disease (CD)] and Primary sclerosing cholangitis (PSC), but the causal association between the two diseases remains unclear.MethodsWe used two-sample Mendelian randomization (MR) to estimate the causal association between IBD and PSC. We chose single nucleotide polymorphisms (SNPs) data for analysis, obtained from previous genome-wide association studies (GWASs). Pleiotropy, heterogeneity, and sensitivity analyses were performed for quality control.ResultsWe found that the causal associations between IBD (both UC and CD) and PSC were significant (e.g., IBD and PSC, Robust adjusted profile score (RAPS) OR = 1.29, 95% CI 1.16∼1.44, p< 0.01; UC and PSC, RAPS OR = 1.40, 95% CI 1.23∼1.58, p< 0.01; CD and PSC, RAPS OR = 1.13, 95% CI 1.02∼1.26, p = 0.02). MR Egger, IVW, and ML tests found statistical heterogeneity between determined IV estimates. The leave-one-out analysis also indicated the sensitivity of the SNPs (e.g., IBD and PSC, MR-Egger Q = 644.30, p< 0.01; UC and PSC, MR-Egger Q = 378.30, p< 0.01; UC and PSC, MR-Egger Q = 538.50, p < 0.01).ConclusionMR analyses support the positive causal effect of IBD (including UC and CD) on PSC in a European population. We provide suggestions for preventing and treating the two diseases.https://www.frontiersin.org/articles/10.3389/fgene.2021.649376/fullinflammatory bowel diseaseulcerative colitisCrohn’s diseasemendelian randomizationprimary sclerosing cholangitis |
| spellingShingle | Ying Xie Xuejie Chen Minzi Deng Yuhao Sun Xiaoyan Wang Jie Chen Changzheng Yuan Therese Hesketh Therese Hesketh Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis Frontiers in Genetics inflammatory bowel disease ulcerative colitis Crohn’s disease mendelian randomization primary sclerosing cholangitis |
| title | Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis |
| title_full | Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis |
| title_fullStr | Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis |
| title_full_unstemmed | Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis |
| title_short | Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis |
| title_sort | causal linkage between inflammatory bowel disease and primary sclerosing cholangitis a two sample mendelian randomization analysis |
| topic | inflammatory bowel disease ulcerative colitis Crohn’s disease mendelian randomization primary sclerosing cholangitis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.649376/full |
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