孟德尔随机化结合转录组鉴定系统性红斑狼疮的关键致病基因
Mendelian randomization combined with transcriptome identification of key causative genes in systemic lupus erythematosus
目的：系统性红斑狼疮(systemic lupus erythematosus，SLE)是一种由免疫系统异常激活引起的慢性弥漫性结缔组织病，深入研究SLE的潜在致病基因具有重要意义。方法：我们分析了（Gene Expression Omnibus，GEO）数据库的四个独立SLE数据集，通过差异表达分析、表达数量性状位点(expression quantitative trait loci，eQTL)分析和孟德尔随机化(Mendelian Randomization，MR)分析评估差异表达基因(differentially expressed genes，DEGs)与SLE之间关系。此外，使用基因集富集分析(Gene Set Enrichment Analysis，GSEA)和基因本体(Gene Ontology，GO)/京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析来探索这些基因的功能作用和通路。最后，使用独立的GEO数据集验证关键基因的可靠性。结果：我们初步鉴定出126个上调DEGs和204个下调DEGs。MR分析鉴定出与SLE相关的五个共表达的关键基因，包括EIF2AK2、IFI44、IFI44L、IFIT1和TCP11L2。此外，CIBERSORT分析表明SLE中存在独特的免疫细胞分布。最后，验证队列与MR分析结果一致，这增强了MR结果的可靠性。结论：筛选出的5个的关键基因可能是SLE的潜在生物标志物，并且TCP11L2表达降低了SLE的发病风险。
Objective: Systemic lupus erythematosus (SLE) is a chronic diffuse connective tissue disease caused by abnormal activation of the immune system. Therefore, it is of great significance to explore the potential pathogenic genes of SLE. Methods: We analyzed four independent SLE datasets from the Gene Expression Omnibus（GEO）database. The evaluation of the relationship between differentially expressed genes (DEGs) and SLE included differential expression analysis, expression quantitative trait loci (eQTL) analysis, and Mendelian randomization (MR) analysis. Additionally, Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays were used to explore the functional roles and pathways of these genes. Finally, the reliability of key genes was verified using an independent GEO dataset. Results: We initially identified 126 up-regulated DEGs and 204 down-regulated DEGs. MR analysis identified five co-expressed key genes associated with SLE, including EIF2AK2, IFI44, IFI44L, IFIT1, and TCP11L2. In addition, CIBERSORT analysis showed the presence of a unique distribution of immune cells in SLE. Finally, the validation cohort was consistent with the MR analysis results, which enhanced the reliability of the MR results. Conclusion: The five key genes may be potential biomarkers of SLE, and TCP11L2 expression reduces the risk of SLE.
宁静华、张 鑫、赵严红、屈 润、张钰哲
基础医学生物科学研究方法、生物科学研究技术
系统性红斑狼疮差异表达基因eQTL分析孟德尔随机化免疫细胞浸润P11L2
Systemic lupus erythematosusdifferentially expressed geneseQTL analysisMendelian randomizationimmune cell infiltrationP11L2
宁静华,张 鑫,赵严红,屈 润,张钰哲.孟德尔随机化结合转录组鉴定系统性红斑狼疮的关键致病基因[EB/OL].(2025-01-20)[2025-06-23].https://www.biomedrxiv.org.cn/article/doi/bmr.202502.00062.点此复制
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