Department of Joint Surgery, HongHui Hospital, Xian Jiaotong University, Xi'an, 710054, Shanxi, China.
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Arthritis Res Ther. 2023 Feb 8;25(1):19. doi: 10.1186/s13075-023-03003-z.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA.
We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein-protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis.
TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified.
By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression.
幼年特发性关节炎（JIA）是儿童中最常见的慢性风湿性疾病，具有遗传易感性和自身免疫、自身炎症等病理过程，但发病机制尚不清楚。我们使用来自大规模全基因组关联研究（GWAS）数据集的表达插值进行全转录组关联研究（TWAS），以鉴定与 JIA 相关的基因、生物途径和环境化学物质。
我们获得了已发表的 JIA GWAS 数据用于 TWAS，并使用 mRNA 表达谱来验证 TWAS 鉴定的基因。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径富集分析。生成了蛋白质-蛋白质相互作用（PPI）网络，并使用分子复合物检测（MCODE）获得了中心基因。最后，从比较毒理学基因组数据库中获得了化学基因表达数据集，用于化学基因组富集分析。
TWAS 鉴定出 1481 个与 JIA 相关的基因，根据 mRNA 表达谱鉴定出 154 个差异表达基因。在比较 TWAS 和 mRNA 表达谱的结果后，我们获得了 8 个重叠基因。TWAS 鉴定基因的 GO 和 KEGG 富集分析产生了 163 条途径，PPI 网络分析和 MCODE 分辨率总共鉴定出 8 个簇。通过化学基因集富集分析，鉴定出 287 种与 JIA 相关的环境化学物质。
通过整合 TWAS 和 mRNA 表达谱，鉴定出与 JIA 相关的基因、生物途径和环境化学物质。我们的研究结果为 JIA 的发病机制提供了新的见解，包括导致其发病和进展的候选遗传和环境因素。
