Expression data from human brain dorsolateral prefrontal cortex - including control samples and samples with major depression disorders (30 samples BA9_F). Homo sapiens

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). Overall design: 30 total samples in 15 pairs were analyzed in postmortem tissue from the dorsolateral 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明确。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 Study, GWAS）已产生了大量与基因及疾病相关的信息，但样本异质性与多种噪声来源仍限制了疾病致病机制的发掘。随着系统性数据集整合的必要性日益凸显，本研究开发了相关分析方法，并对11项针对重度抑郁症患者与非精神疾病对照受试者的死后大脑组织的基因共表达关联研究开展了元聚类分析。随后，我们对经元分析得到的前50个共表达模块进行富集分析，以探究其中是否富集了针对各类疾病的GWAS所鉴定的基因。最终发现一个包含88个基因的共表达模块，可稳定且显著地关联到重度抑郁症、其他神经精神疾病与脑功能相关的GWAS结果，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（详细内容请参见已发表论文）。实验整体设计：本研究共纳入30份样本，分为15对，所有样本均来自背外侧前额叶皮层的死后脑组织。