炎症性肠病与脑白质微观结构：双向孟德尔随机化研究。

Inflammatory bowel disease and white matter microstructure: A bidirectional Mendelian randomization study.

机构信息

School of Medical Technology, School of Medical Imaging, Tianjin Medical University, Tianjin, China.

出版信息

Brain Res. 2024 Dec 15;1845:149206. doi: 10.1016/j.brainres.2024.149206. Epub 2024 Aug 28.

DOI:10.1016/j.brainres.2024.149206

PMID:39208967

Abstract

BACKGROUND

Observational studies have reported changes in the brain white matter (WM) microstructure in patients with inflammatory bowel disease (IBD); however, it remains uncertain whether the relationship between them is causative. The aim of this study is to reveal the potential causal relationship between IBD and WM microstructure through a bidirectional two-sample Mendelian randomization (MR) analysis.

METHODS

We extracted genome-wide association study (GWAS) summary statistics for IBD and WM microstructure from published GWASs. Two-sample MR analysis was conducted to explore the bidirectional causal associations between IBD and WM microstructure, followed by a series of sensitivity analyses to assess the robustness of the results.

RESULTS

Although forward MR analysis results showed no evidence of causality from microstructural WM to IBD, reverse MR showed that genetically predicted IBD, consisting of ulcerative colitis and Crohn's disease, has a significant causal effect on the orientation dispersion index (OD) of the right tapetum (β = -0.029, 95% CI = -0.045 to -0.013, p = 3.63 × 10). Further sensitivity analysis confirmed the robustness of the association.

CONCLUSION

Our results suggested the potentially causal association of IBD with reduced OD in the right tapetum.

摘要

背景

观察性研究报告称炎症性肠病（IBD）患者的脑白质（WM）微观结构发生变化；然而，目前尚不确定它们之间的关系是否具有因果关系。本研究旨在通过双向两样本 Mendelian 随机分析（MR）揭示 IBD 和 WM 微观结构之间潜在的因果关系。

方法

我们从已发表的 GWAS 中提取了 IBD 和 WM 微观结构的全基因组关联研究（GWAS）汇总统计数据。进行两样本 MR 分析以探索 IBD 和 WM 微观结构之间的双向因果关系，然后进行一系列敏感性分析以评估结果的稳健性。

结果

虽然正向 MR 分析结果表明微观结构 WM 对 IBD 没有因果关系的证据，但反向 MR 表明，遗传预测的 IBD（包括溃疡性结肠炎和克罗恩病）对右侧脉络丛的方位分散指数（OD）有显著的因果影响（β = -0.029，95%CI = -0.045 至 -0.013，p = 3.63×10）。进一步的敏感性分析证实了该关联的稳健性。