Mendelian randomization study of inflammatory bowel disease and bone mineral density
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RESEARCH ARTICLE
Open Access
Mendelian randomization study of inflammatory bowel disease and bone mineral density Fashuai Wu1*, Yu Huang2, Jialu Hu3* and Zengwu Shao1*
Abstract Background: Recently, the association between inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) and BMD has attracted great interest in the research community. However, the results of the published epidemiological observational studies on the relationship between inflammatory bowel disease and BMD are still inconclusive. Here, we performed a two-sample Mendelian randomization analysis to investigate the causal link between inflammatory bowel disease and level of BMD using publically available GWAS summary statistics. Methods: A series of quality control steps were taken in our analysis to select eligible instrumental SNPs which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighting, MR-PRESSO method, mode-based estimate method, weighted median, MR-Egger regression, and MR.RAPS method) that are based on different assumptions of twosample MR analysis. The MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on BMD. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy. Results: Our two-sample Mendelian randomization analysis with two groups of exposure GWAS summary statistics and four groups of outcome GWAS summary statistics suggested a definitively causal effect of genetically predicted ulcerative colitis on TB-BMD and FA-BMD but not on FN-BMD or LS-BMD (after Bonferroni correction), and we merely determined a causal effect of Crohn’s disease on FN-BMD but not on the others, which was somewhat inconsistent with many published observational researches. The causal effect of inflammatory bowel disease on TBBMD was significant and robust but not on FA-BMD, FN-BMD, and LS-BMD, which might result from the cumulative effect of ulcerative colitis and Crohn’s disease on BMDs. (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected] 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 3 School of Computer Science, Northwestern Polytechnical University, West Youyi Road 127, Xi’an 710072, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other thir
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