1.2. Gene Expression in Schizophrenia, Major Depression, and Bipolar Disorder
The correlated expression of genes in brain or in peripheral tissues forms a co-expression network. Gene−gene expression correlation matrices can be built into coherent network connections. An expression quantitative trait locus (eQTL) study of a developing brain series mapped the significant loci to co-expression networks that were highly enriched for significant GWAS findings in schizophrenia [20]. The co-expression network was formed around a hub of several interconnected MHC genes, increasing interest to find the truly causative genes, and not merely candidate genes.
A second gene expression co-network of a module of genes that was differentially expressed between SZ and controls in whole blood also formed a network involving the MHC locus [20]. This co-expression network module was independent of antipsychotic medication in SZ subjects, and included multiple members of the MHC locus: heat shock protein 90 kDa α (cytosolic), class B member 1 (HSP90AB1); ring finger protein 1 (RING1); casein kinase 2, β polypeptide (CSNK2B); tubulin, β (TUBB); and ATP-binding cassette, sub-family F, member 1 (ABCF1). These two studies show the feasibility of expression studies to inform existing GWASes of differential regulation in brain and whole blood.
Microarray, quantitative PCR (qPCR) and RNA (cDNA) sequencing are useful techniques that examine gene expression in biological samples. The experiments that are reported begin with an inquiry into bipolar disorder using Affymetrix human exon 1.0 ST microarrays, to compare a matched cohort of bipolar type I subjects to controls using anterior cingulate cortex postmortem samples. The anterior cingulate is a region profoundly implicated in mood dysregulation. To validate the exon microarray results, qPCR experiments were performed in a larger cohort using five different brain regions, cell lines, and blood samples.