Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Front Immunol. 2024 Jan 9;14:1322673. doi: 10.3389/fimmu.2023.1322673. eCollection 2023.
Although a correlation between immune cell phenotypes and inflammatory bowel disease (IBD) has been established, a causal relationship remains unestablished.
To assess causal associations between immune cell phenotypes and IBD and its subtypes, we employed Mendelian randomization (MR) methods and genome-wide association studies (GWAS) summary statistics. The primary outcomes were determined based on the inverse variance weighting (IVW) results, with the assessment of heterogeneity and pleiotropy conducted through Cochrane's Q-test and MR-Egger. The stability of the MR results was then examined using leave-one-out analysis, and false discovery rate (FDR) correction was applied to evaluate the strength of the causal relationship between exposure and outcome. Furthermore, to identify immunophenotypes strongly associated with IBD, a meta-integration of the effect values of all positive results in both datasets was conducted.
The analysis of 731 immune cell phenotypes and IBD using MR techniques revealed potential causal associations between 26 phenotypes and IBD. Subsequent meta-integration of the two datasets provided evidence of solid causal associations between 18 immune phenotypes and IBD and its subtypes. Nominal causal associations were also identified in the remaining eight immune phenotypes and IBD and its subtypes.
Our study confirms causal solid associations between 18 immune phenotypes and IBD, thus guiding future clinical studies.
虽然已经确定了免疫细胞表型与炎症性肠病（IBD）之间存在相关性，但尚未确定因果关系。
为了评估免疫细胞表型与 IBD 及其亚型之间的因果关联，我们采用了孟德尔随机化（MR）方法和全基因组关联研究（GWAS）汇总统计数据。主要结局是根据逆方差加权（IVW）结果确定的，通过 Cochrane's Q 检验和 MR-Egger 评估异质性和多效性。然后通过单因素剔除分析检查 MR 结果的稳定性，并应用错误发现率（FDR）校正来评估暴露与结局之间因果关系的强度。此外，为了确定与 IBD 强烈相关的免疫表型，对两个数据集所有阳性结果的效应值进行了荟萃整合。
使用 MR 技术对 731 种免疫细胞表型和 IBD 进行分析，发现 26 种表型与 IBD 之间存在潜在的因果关联。随后对两个数据集的荟萃整合提供了证据，表明 18 种免疫表型与 IBD 及其亚型之间存在确凿的因果关联。在其余 8 种免疫表型和 IBD 及其亚型中也发现了名义上的因果关联。
我们的研究证实了 18 种免疫表型与 IBD 之间存在因果关系，这为未来的临床研究提供了指导。
