The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Frontiers in Immunology

Immunology

Dengyong Xu¹  Weidong Xie²  Jiaying Shen³  Yao Chen³  Binbin Xie³  Xing Gao⁴  Guang Yang⁵  Ya Wang⁶ 

[1] Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China;Department of Orthopedic Surgery, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China;Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China;Department of Hospital Infection-Control, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China;Department of Hospital Infection-Control, Zhejiang Cancer Hospital, Hangzhou, China;

关键词: ulcerative colitis;    Crohn’s disease;    inflammatory bowel disease;    bone mineral density;    osteoporosis;    Mendelian randomization;   

DOI  :  10.3389/fimmu.2023.1148107

 received in 2023-01-19, accepted in 2023-05-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundMany existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics.MethodsSummary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated.ResultsIn the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019).ConclusionOur study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

【 授权许可】

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Copyright © 2023 Xu, Chen, Gao, Xie, Wang, Shen, Yang and Xie