Xu Yong, Yao Shugart Yin, Wang Guoqiang, Cheng Zaohuo, Jin Chunhui, Zhang Kai, Wang Jun, Yu Hao, Yue Weihua, Zhang Fuquan, Zhang Dai
Department of Psychiatry, First Hospital /First Clinical Medical College of Shanxi Medical University, Taiyuan, China.
Unit on Statistical Genomics, Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
Sci Rep. 2016 Jan 6;6:16767. doi: 10.1038/srep16767.
To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ.
为了识别精神分裂症（SZ）中的基因表达异常，我们使用微阵列技术对18例早发性SZ患者和12名对照者的外周血单核细胞（PBMC）进行全基因组基因表达谱分析。我们检测到84个转录本因诊断状态而差异表达，其中82个基因上调，2个基因下调。我们鉴定出两个与SZ相关的基因共表达模块（绿色和红色），包括446个基因。绿色模块与SZ呈正相关，主要包含SZ中上调的基因；而红色模块与疾病状态呈负相关，主要涉及SZ中名义上下调的基因。嗅觉转导通路是这两个模块内基因最富集的通路。使用实时定量PCR验证了包括AKT1、BRCA1、CCDC134、UBD和ZIC2在内的几个枢纽基因的表达水平。我们的研究结果表明，mRNA共表达异常可能是SZ发病机制的一个有前景的机制。
