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炎症性肠病与乳糜泻:一项双向孟德尔随机化研究。

Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study.

作者信息

Shi Yue, Feng Sijia, Yan Mengdie, Wei Shuyan, Yang Kejia, Feng Yue

机构信息

Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Front Genet. 2022 Aug 19;13:928944. doi: 10.3389/fgene.2022.928944. eCollection 2022.

Abstract

Although previous epidemiological studies have reported substantial links between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and celiac disease (CeD), the causal relationship between the two remains unknown. The purpose of the current study was to evaluate the bidirectional causation between IBD and CeD using Mendelian randomization (MR). We obtained genome-wide association study (GWAS) summary data of IBD (CD and UC) and CeD of thoroughly European ancestry from the IEU GWAS database. We screened eligible instrumental variables (IVs) according to the three assumptions of MR. MR was performed using MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods. The MR-Egger intercept and MR-PRESSO method investigated the horizontal pleiotropy effect. A leave-one-out analysis was performed to prevent bias caused by a single SNP. The study assessed a bidirectional causal effect between CD and CeD; CD increased the risk of CeD (IVW odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.19-1.35, = 3.75E-13) and vice-a-versa (IVW OR = 1.09, 95% CI = 1.05-1.13, = 1.39E-05). Additionally, CeD was influenced by IBD (IVW OR = 1.24, 95% CI = 1.16-1.34, = 9.42E-10) and UC (IVW OR = 0.90, 95% CI = 0.83-0.98, = 0.017). However, we observed no evidence of a causal relationship between CeD and IBD (IVW OR = 1.00, 95% CI = 0.97-1.04, = 0.900) or UC (IVW OR = 0.96, 95% CI = 0.92-1.02, = 0.172). The present study revealed that IBD and CeD have a bidirectional causal relationship. However, it is slightly different from the results of previous observational studies, recommending that future studies focus on the mechanisms of interaction between CD and CeD.

摘要

尽管先前的流行病学研究报告了炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),与乳糜泻(CeD)之间存在显著关联,但两者之间的因果关系仍不明确。本研究的目的是使用孟德尔随机化(MR)评估IBD和CeD之间的双向因果关系。我们从IEU GWAS数据库中获取了具有完全欧洲血统的IBD(CD和UC)和CeD的全基因组关联研究(GWAS)汇总数据。我们根据MR的三个假设筛选了合格的工具变量(IV)。使用MR-Egger、加权中位数(WM)和逆方差加权(IVW)方法进行MR分析。MR-Egger截距和MR-PRESSO方法研究了水平多效性效应。进行了留一法分析以防止单个单核苷酸多态性(SNP)引起的偏差。该研究评估了CD和CeD之间的双向因果效应;CD增加了CeD的风险(IVW优势比(OR)=1.27,95%置信区间(CI)=1.19-1.35,P=3.75E-13),反之亦然(IVW OR=1.09,95%CI=1.05-1.13,P=1.39E-05)。此外,CeD受IBD(IVW OR=1.24,95%CI=1.16-1.34,P=9.42E-10)和UC(IVW OR=0.90,95%CI=0.83-0.98,P=0.017)的影响。然而,我们未观察到CeD与IBD(IVW OR=1.00,95%CI=0.97-1.04,P=0.900)或UC(IVW OR=0.96,95%CI=0.92-1.02,P=0.172)之间存在因果关系的证据。本研究表明IBD和CeD存在双向因果关系。然而,这与先前观察性研究的结果略有不同,建议未来的研究关注CD和CeD之间的相互作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b0/9437575/cf7d743a012e/fgene-13-928944-g001.jpg

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