Expression data from human brain orbital ventral prefrontal cortex - including control samples and samples with major depression disorders (24 samples NY_BA47)

Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). 24 total samples in 12 pairs were analyzed in postmortem tissue from the orbital ventral prefrontal cortex.

重度抑郁症（Major Depressive Disorder, MDD）是一种异质性疾病，其病理机制大多尚未阐明。大规模基因表达（转录组，transcriptome）分析以及针对单核苷酸多态性（Single Nucleotide Polymorphisms）的全基因组关联研究（Genome-Wide Association Studies, GWAS）已积累了大量基因与疾病相关的研究数据，但异质性与多种噪声来源制约了疾病致病机制的解析。随着系统性数据集整合逐渐成为研究刚需，我们开发了专属分析方法，并针对11项转录组研究中的基因共表达关联开展元聚类分析，这些研究的样本均来自重度抑郁症（MDD）患者与非精神疾病对照受试者的死后脑组织。随后，我们针对各类疾病的GWAS所鉴定的关联基因，在元分析得到的前50个共表达模块中开展富集分析。结果显示，包含88个基因的共表达模块，与MDD、其他神经精神疾病及脑功能相关的GWAS结果存在显著且一致的关联，同时也与临床抑郁风险升高的内科疾病相关，但与其他疾病无显著关联（详细内容请参阅发表文献）。本研究共分析了12对总计24份眶腹前额叶皮层的死后组织样本。