A comprehensive regional analysis of genome-wide expression profiles for major depressive disorder

Diego A. Forero, Gina P. Guio-Vega, Yeimy González-Giraldo

Major depressive disorder (MDD) is a global health challenge. In recent years, a large number of genome-wide expression studies (GWES) have been carried out to identify the transcriptomic profiles for MDD. The objective of this work was to carry out a comprehensive meta-analysis of available GWES for MDD. GWES for MDD with available raw data were searched in NCBI GEO, Array Express and Stanley databases. Raw GWES data were preprocessed and normalized and meta-analytical procedures were carried out with the Network Analyst program. 743 samples from 24 primary studies were included in our meta-analyses for blood (Blo), amygdala (Amy), cerebellum (Cer), anterior cingulate cortex (ACC) and prefrontal cortex (PFC) regions. A functional enrichment analysis was carried out. We identified 35, 793, 231, 668 and 252 differentially expressed (DE) genes for Blo, Amy, Cer, ACC and PFC regions. A region-dependent significant enrichment for several functional categories, such as gene ontologies, signaling pathways and topographic parameters, was identified. There was convergence with other available genome-wide studies, such as GWAS, DNA methylation analyses and miRNA expression studies. Raw data were not available for several primary studies that have been published previously. This is the largest meta-analysis for GWES in MDD. The examination of convergence of genome-wide evidence and of the functional enrichment analysis provides a global overview of potential neural signaling mechanisms dysregulated in MDD. Our comprehensive analysis of several brain regions identified lists of DE genes for MDD that are interesting candidates for further studies.