Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Immunol. 2023 May 18;14:1148107. doi: 10.3389/fimmu.2023.1148107. eCollection 2023.
Many 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.
Summary 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.
In 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).
Our 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.
许多现有研究表明，炎症性肠病（IBD）患者，包括溃疡性结肠炎（UC）和克罗恩病（CD），往往存在全身骨矿物质密度（BMD）低的风险，并且更容易患有骨质疏松症（OS）。为了确定 IBD 与骨代谢紊乱之间的因果关系，我们使用公开可用的汇总统计数据进行了两样本孟德尔随机化分析（TSMR）。
从开放基因组全基因组关联研究（GWAS）、芬兰人群和国际炎症性肠病遗传联盟（IIBDGC）中下载了全身 BMD、OS 和 IBD 的汇总统计数据。本孟德尔随机化（MR）工作包括欧洲和东亚人群。进行了一系列质量控制程序来选择与全身 BMD、OS 和 IBD 密切相关的合格工具 SNP。为了使结论更可靠，我们应用了五种稳健的分析方法，其中逆方差加权（IVW）方法作为主要方法。此外，还评估了异质性、多效性和敏感性。
在欧洲人群中，UC 对全身 BMD 的遗传关联（OR=0.97，95%CI=0.96，0.99，P<0.001）和整体 IBD 对全身 BMD 的遗传关联（OR=0.98，95%CI=0.97，1.00，P=0.013）具有统计学意义，而 CD 对全身 BMD 的影响则不够显著（OR=0.99，95%CI=0.98，1.00，P=0.085）。UC、CD 和整体 IBD 都可以成为患有病理性骨折的 OS 的遗传危险因素（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，整体 IBD：OR=1.13，95%CI=1.02，1.24，P=0.015）。在东亚人群中，只有 CD 与 OS 有因果关系（OR=1.04，95%CI=1.01，1.07，P=0.019）。
我们的研究揭示了欧洲和东亚人群中 IBD 与全身 BMD 和 OS 之间存在遗传相关性。这项工作补充了之前回顾性研究的结果，并表明 IBD 患者有必要进行 BMD 监测。
Zotero 插件
