炎症性肠病与结节性红斑之间的因果关系：两样本双向孟德尔随机化研究。

Causal relationship between inflammatory bowel disease and erythema nodosum: A two-sample bidirectional Mendelian randomization study.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Gastroenterology, Wenzhou Central Hospital, Wenzhou, Zhejiang, China.

出版信息

Skin Res Technol. 2024 Feb;30(2):e13600. doi: 10.1111/srt.13600.

DOI:10.1111/srt.13600

PMID:38297958

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10831198/

Abstract

BACKGROUND

Previous studies have demonstrated the coexistence of erythema nodosum (EN) and inflammatory bowel disease (IBD), while the exact etiology of the co-occurrence of the two disorders remains uncertain.

METHODS

A bidirectional two-sample Mendelian randomization (MR) design was employed to determine the causal link between EN and IBD. Genetic variations associated with Crohn's disease (CD) and ulcerative colitis (UC) were derived from accessible genome-wide association studies pertaining to European ancestry. The FinnGen database was used to find the genetic variations containing EN. In the forward model, IBD was identified as the exposure, whereas in the reverse model, EN was identified as the exposure. The causal link between IBD and EN was examined using a range of different analysis techniques, the primary one being the inverse variance weighted (IVW) method, including inverse variance weighted-fixed effects (IVW-FE) and inverse-variance weighted-multiplicative random effects (IVW-MRE). To strengthen the results, assessments of sensitivity, heterogeneity, and pleiotropy were also conducted.

RESULTS

MR results showed that IBD increased the risk of EN (IVW-MRE: OR = 1.242, 95% CI = 1.068-1.443, p = 0.005). Furthermore, there was a strong correlation found between CD and a higher risk of EN (IVW-FE: OR = 1.250, 95% CI = 1.119-1.396, p = 8.036 × 10 ). However, UC did not appear to be linked to EN (IVW-FE: OR = 1.104, 95% CI = 0.868-1.405, p = 0.421). The reverse MR analysis findings did not imply that EN was linked to IBD. Horizontal pleiotropy did not appear to exist, and the robustness of these findings was confirmed.

CONCLUSION

The current investigation found that in European populations, IBD and its subtype CD could raise the incidence of EN.

摘要

背景

先前的研究表明结节性红斑（EN）和炎症性肠病（IBD）共存，而这两种疾病同时发生的确切病因仍不确定。

方法

采用双向两样本孟德尔随机化（MR）设计来确定 EN 与 IBD 之间的因果关系。与欧洲血统相关的可及全基因组关联研究中得出了与克罗恩病（CD）和溃疡性结肠炎（UC）相关的遗传变异。FinnGen 数据库用于找到包含 EN 的遗传变异。在前向模型中，IBD 被视为暴露因素，而在反向模型中，EN 被视为暴露因素。采用多种不同的分析技术来检验 IBD 和 EN 之间的因果关系，主要是逆方差加权（IVW）法，包括逆方差加权固定效应（IVW-FE）和逆方差加权乘法随机效应（IVW-MRE）。为了加强结果，还进行了敏感性、异质性和多效性评估。

结果

MR 结果表明，IBD 增加了发生 EN 的风险（IVW-MRE：OR=1.242，95%CI=1.068-1.443，p=0.005）。此外，发现 CD 与 EN 发生风险增加之间存在很强的相关性（IVW-FE：OR=1.250，95%CI=1.119-1.396，p=8.036×10-8）。然而，UC 似乎与 EN 无关（IVW-FE：OR=1.104，95%CI=0.868-1.405，p=0.421）。反向 MR 分析结果表明，EN 与 IBD 无关。不存在水平多效性，这些发现的稳健性得到了确认。