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动脉粥样硬化与炎症性肠病风险之间的因果关系:一项两样本孟德尔随机化研究。

Causal relationship between atherosclerosis and inflammatory bowel disease risk: a two-sample Mendelian randomization study.

作者信息

Guo Wenjuan, Peng Na, Du Shiyu

机构信息

Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghuadong Street, 100029, Beijing, China.

出版信息

Thromb J. 2025 Apr 23;23(1):39. doi: 10.1186/s12959-025-00722-y.

Abstract

OBJECTIVE

This study was to evaluate the causal associations of atherosclerosis with the risk of inflammatory bowel disease (IBD), and its subtypes [ulcerative colitis (UC) and Crohn's disease (CD)]: a two-sample Mendelian randomization study.

MATERIALS AND METHODS

Single nucleotide polymorphism (SNPs) associated with atherosclerosis including CPAmax, CPSmax, brachial-femoral pulse wave velocity (bfPWV), coronary atherosclerosis, cerebral atherosclerosis, peripheral atherosclerosis, coronary artery disease (CAD) and ischemic stroke (IS) were identified from previous genome-wide association studies (GWAS). SNPs were strictly selected to fulfill the MR assumptions. The causal links between atherosclerosis and IBD were evaluated using inverse-variance weighted (IVW) as the primary method. Leave-one-out analysis was utilized to evaluate whether the outcomes were attributable to any individual SNP correlated to sex hormones. The estimates were subjected to odds ratio (OR) and 95% confidence interval (CI).

RESULTS

The results of IVW revealed that coronary atherosclerosis had causal association with increased risk of CD (OR = 1.162, 95%CI: 1.031-1.311). The causal association was also observed in IS with CD (OR = 1.376, 95%CI: 1.011-1.873) and UC (OR = 1.508, 95%CI: 1.153-1.971). Leave-one-out analysis indicated that no single SNP can affect the associations of CAD with IBD, CD, and UC, coronary atherosclerosis with CD, as well as IC with CD and UC.

CONCLUSIONS

Coronary atherosclerosis was causally related to CD, and IS had causal relationship with CD and UC. The finding might provide evidence for future exploration of the etiology for IBD.

摘要

目的

本研究旨在评估动脉粥样硬化与炎症性肠病(IBD)及其亚型[溃疡性结肠炎(UC)和克罗恩病(CD)]风险之间的因果关联:一项两样本孟德尔随机化研究。

材料与方法

从既往全基因组关联研究(GWAS)中鉴定出与动脉粥样硬化相关的单核苷酸多态性(SNP),包括CPAmax、CPSmax、肱股脉搏波速度(bfPWV)、冠状动脉粥样硬化、脑动脉粥样硬化、外周动脉粥样硬化、冠状动脉疾病(CAD)和缺血性卒中(IS)。严格选择SNP以满足孟德尔随机化假设。采用逆方差加权(IVW)作为主要方法评估动脉粥样硬化与IBD之间的因果联系。采用留一法分析评估结果是否归因于与性激素相关的任何单个SNP。估计值采用比值比(OR)和95%置信区间(CI)表示。

结果

IVW结果显示,冠状动脉粥样硬化与CD风险增加存在因果关联(OR = 1.162,95%CI:1.031 - 1.311)。在IS与CD(OR = 1.376,95%CI:1.011 - 1.873)以及UC(OR = 1.508,95%CI:1.153 - 1.971)之间也观察到因果关联。留一法分析表明,没有单个SNP能影响CAD与IBD、CD和UC、冠状动脉粥样硬化与CD以及IS与CD和UC之间的关联。

结论

冠状动脉粥样硬化与CD存在因果关系,IS与CD和UC存在因果关系。这一发现可能为未来探索IBD的病因提供证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce78/12020298/419c44c57530/12959_2025_722_Fig4_HTML.jpg

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