Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis
IntroductionOver the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdepende...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1151837/full |
| _version_ | 1827940813500317696 |
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| author | Zhujiang Dai Zhujiang Dai Weimin Xu Weimin Xu Rui Ding Rui Ding Xiang Peng Xiang Peng Xia Shen Xia Shen Jinglue Song Jinglue Song Peng Du Peng Du Zhongchuan Wang Zhongchuan Wang Yun Liu Yun Liu |
| author_facet | Zhujiang Dai Zhujiang Dai Weimin Xu Weimin Xu Rui Ding Rui Ding Xiang Peng Xiang Peng Xia Shen Xia Shen Jinglue Song Jinglue Song Peng Du Peng Du Zhongchuan Wang Zhongchuan Wang Yun Liu Yun Liu |
| author_sort | Zhujiang Dai |
| collection | DOAJ |
| description | IntroductionOver the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.MethodsWe validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization.ResultsGenetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively.ConclusionWe demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease. |
| first_indexed | 2024-03-13T09:28:02Z |
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| id | doaj.art-43f97ce4f28b45e88d941b47a98bd1df |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-13T09:28:02Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-43f97ce4f28b45e88d941b47a98bd1df2023-05-26T04:59:41ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-05-011110.3389/fpubh.2023.11518371151837Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosisZhujiang Dai0Zhujiang Dai1Weimin Xu2Weimin Xu3Rui Ding4Rui Ding5Xiang Peng6Xiang Peng7Xia Shen8Xia Shen9Jinglue Song10Jinglue Song11Peng Du12Peng Du13Zhongchuan Wang14Zhongchuan Wang15Yun Liu16Yun Liu17Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaShanghai Colorectal Cancer Research Center, Shanghai, ChinaIntroductionOver the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.MethodsWe validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization.ResultsGenetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively.ConclusionWe demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1151837/fullinflammatory bowel diseaseosteoporosisMendelian randomizationcausal associationGWAS |
| spellingShingle | Zhujiang Dai Zhujiang Dai Weimin Xu Weimin Xu Rui Ding Rui Ding Xiang Peng Xiang Peng Xia Shen Xia Shen Jinglue Song Jinglue Song Peng Du Peng Du Zhongchuan Wang Zhongchuan Wang Yun Liu Yun Liu Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis Frontiers in Public Health inflammatory bowel disease osteoporosis Mendelian randomization causal association GWAS |
| title | Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| title_full | Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| title_fullStr | Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| title_full_unstemmed | Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| title_short | Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| title_sort | two sample mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis |
| topic | inflammatory bowel disease osteoporosis Mendelian randomization causal association GWAS |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1151837/full |
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