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哮喘与炎症性肠病之间的因果关系:两样本双向孟德尔随机化分析。

Causal relationship between asthma and inflammatory bowel disease : A two-sample bidirectional mendelian randomization analysis.

机构信息

Department of General Surgery, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang 621054, Sichuan Province, China.

Department of General Surgery, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang 621054, Sichuan Province, China.

出版信息

Heart Lung. 2024 Jan-Feb;63:108-113. doi: 10.1016/j.hrtlng.2023.10.004. Epub 2023 Oct 14.

Abstract

BACKGROUND

Based on the findings of current observational studies, asthma and inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are associated; however, their causal association cannot be established due to methodological limitations.

OBJECTIVES

we use two-sample bidirectional mendelian randomization (MR) to overcome the confounding factors and explore the causal link between asthma and inflammatory bowel disease.

METHODS

After selecting asthma and IBD-related genome-wide association studies (GWAS) data and screening single nucleotide polymorphisms (SNPs), MR analysis was performed by four methods: inverse variance weighted (IVW), MR-Egger, maximum likelihood, and weighted median (WM), while Cochran's Q test was used to detect heterogeneity and MR-Egger intercept to detect horizontal pleiotropy. Finally, we used the leave-one-out method and funnel plot to perform sensitivity analysis.

RESULTS

We screened 57, 59, and 60 SNPs in the association analysis of asthma and IBD, CD, and UC, respectively. The results of MR analysis showed that asthma only increased the risk of CD (IVW: OR = 1.1712, 95% CI = 1.0418-1.3167, P value = 0.0082; maximum likelihood: OR = 1.1739, 95% CI = 1.0428-1.3215, P value = 0.0080). Neither forward nor reverse MR analysis revealed heterogeneity or horizontal pleiotropy. Similarly, we did not find potential directional pleiotropy by funnel plot, and the leave-one-out method did not suggest a significant effect of a single SNP on the overall results.

CONCLUSIONS

we found a negative correlation between asthma and Crohn's disease, but more research is needed to confirm this.

摘要

背景

基于当前观察性研究的结果,哮喘和炎症性肠病(包括克罗恩病和溃疡性结肠炎)之间存在关联;然而,由于方法学的限制,无法确定它们之间的因果关系。

目的

我们使用两样本双向孟德尔随机化(MR)来克服混杂因素,并探讨哮喘和炎症性肠病之间的因果关系。

方法

在选择哮喘和 IBD 相关的全基因组关联研究(GWAS)数据和筛选单核苷酸多态性(SNP)后,我们通过四种方法进行 MR 分析:逆方差加权(IVW)、MR-Egger、最大似然和加权中位数(WM),同时使用 Cochran's Q 检验检测异质性,使用 MR-Egger 截距检测水平多效性。最后,我们使用逐一剔除法和漏斗图进行敏感性分析。

结果

我们在哮喘与 IBD、CD 和 UC 的关联分析中分别筛选了 57、59 和 60 个 SNP。MR 分析结果表明,哮喘仅增加了 CD 的发病风险(IVW:OR=1.1712,95%CI=1.0418-1.3167,P 值=0.0082;最大似然:OR=1.1739,95%CI=1.0428-1.3215,P 值=0.0080)。无论是正向还是反向 MR 分析都没有发现异质性或水平多效性。同样,我们也没有通过漏斗图发现潜在的方向性多效性,逐一剔除法也没有提示单个 SNP 对整体结果有显著影响。

结论

我们发现哮喘与克罗恩病之间存在负相关,但需要进一步的研究来证实这一点。

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