Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis.
Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis.
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DOI：
10.3389/fpubh.2023.1151837
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发表时间：
2023
影响因子：
5.2
通讯作者：
Liu, Yun
中科院分区：
文献类型：
--
作者：
Dai, Zhujiang;Xu, Weimin;Ding, Rui;Peng, Xiang;Shen, Xia;Song, Jinglue;Du, Peng;Wang, Zhongchuan;Liu, Yun
在过去的几年中，多项观察性研究推测炎症性肠病（IBD）（包括溃疡性结肠炎（UC）和克罗恩病（CD））与骨质疏松症之间存在潜在的相关性。然而，尚未就其相互依赖性和发病机制达成共识。在此，我们试图进一步探讨它们之间的因果关系。我们基于全基因组关联研究（GWAS）数据验证了IBD与人类骨密度降低之间的关联。为了研究IBD和骨质疏松症之间的因果关系，我们使用训练集和验证集进行了一项双样本孟德尔随机化研究。IBD、CD、UC和骨质疏松症的遗传变异数据来自已发表的欧洲血统个体的全基因组关联研究。经过一系列稳健的质量控制步骤后，我们纳入了与暴露（IBD/CD/UC）显著相关的合格工具变量（SNP）。采用MR Egger法、加权中位数法、逆方差加权法、简单模式法和加权模式法等5种算法对IBD与骨质疏松症的因果关系进行推断。此外，我们还通过异质性检验、多效性检验、留一法敏感性检验和多变量孟德尔随机化分析来评估孟德尔随机化分析的稳健性。遗传预测CD与骨质疏松风险呈正相关，在训练集和验证集中CD的OR分别为1.060（95% CI 1.016，1.106; p = 0.007）和1.044（95% CI 1.002，1.088; p = 0.039）。然而，孟德尔随机化分析未显示UC与骨质疏松症之间存在显著的因果关系（p > 0.05）。此外，我们发现总体IBD与骨质疏松症预测相关，在训练集和验证集中OR分别为1.050（95% CI 0.999，1.103; p = 0.055）和1.063（95% CI 1.019，1.109; p = 0.005）。我们证明了CD和骨质疏松症之间的因果关系，补充了易患自身免疫性疾病的遗传变异的框架。
Over 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. We 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. Genetically 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. We demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
7
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Cheng H;Garrick DJ;Fernando RL
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Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
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Thompson JR
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Ference BA;Majeed F;Penumetcha R;Flack JM;Brook RD
通讯作者：
Brook RD
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4.3
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de Silva, Aduna Priyadarsin;Karunanayake, Aranjan Lionel;de Silva, Hithanadura Janaka
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de Silva, Hithanadura Janaka