UNASSIGNED: Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database.
UNASSIGNED: Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD.
UNASSIGNED: We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.
■从基因表达综合(GEO)数据库获得IBD和NAFLD的基因芯片数据集。进行加权基因共表达网络分析(WGCNA)以鉴定与IBD和NAFLD相关的那些数据集中的模块。ClueGO用于IBD和NAFLD之间共享基因的生物学分析。基于人类microRNA疾病数据库(HMDD),获得NAFLD和IBD常见的microRNA(miRNA)。使用miRTarbase预测miRNA的潜在靶基因,miRDB,和TargetScan数据库。使用来自开放数据库的GWAS的数据,使用双样本孟德尔随机化(MR)和双向MR来探索白细胞介素-17(IL-17)与IBD和NAFLD风险之间的因果关系。
■通过WGCNA,鉴定了感兴趣的基因模块。用ClueGO进行GO富集分析提示趋化因子的异常分泌可能是IBD和NAFLD的共同病理生理特征,IL-17相关通路可能是IBD和NAFLD发生病理变化的共同关键通路。鉴定了IBD和NAFLD中的核心差异表达基因(DEGs),包括COL1A1,LUM,CCL22、CCL2、THBS2、COL1A2、MMP9和CXCL8。另一个队列用于验证。最后,miRNA的分析确定了潜在的治疗靶标。MR结果表明,尽管IBD和NAFLD之间没有因果关系,IL-17与IBD和NAFLD之间存在因果关系。
■我们建立了一个共病模型来解释IBD合并NAFLD的潜在机制,并确定了细胞因子IL-17介导的趋化因子相关途径是IBD合并NAFLD的核心途径,其中miRNA也发挥作用,因此提供了潜在的治疗靶标。