Jia Keyu, Shen Jun
Laboratory of Medicine, Baoshan Branch, Ren Ji Hospital, School of Medicine, Nephrology department, Shanghai Jiao Tong University, 1058 Huanzhen Northroad, Shanghai, 200444, China.
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Research Center, Ren Ji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.
Cell Biosci. 2024 Feb 25;14(1):29. doi: 10.1186/s13578-024-01204-w.
Crohn's disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.
克罗恩病（CD）被视为一种影响肠道所有节段和多个器官的终身进展性疾病。基于全基因组关联研究（GWAS）和基因表达数据，全转录组关联研究（TWAS）有助于识别与发病机制和疾病行为相关的易感基因。在本综述中，我们概述了七项已报道的CD的TWAS研究，总结了它们的研究设计，并讨论了TWAS中使用的影响易感基因优先级排序的关键方法和步骤。本文总结了CD组织特异性易感基因的筛选，并讨论了在特定组织类型中报道的与CD相关的重叠易感基因的潜在病理机制。通过对易感基因进行基因本体（GO）通路富集分析，我们观察到回肠脂质相关代谢和结肠细胞外囊泡可能参与CD的发病机制。我们进一步指出了与CD相关的TWAS的低重复性，并讨论了这些问题的原因、解决策略。未来，需要设计更多的TWAS纳入大规模、统一的队列、统一的分析流程以及充分分类的表达性状位点数据库。
