A DRD2 CO-EXPRESSION GENE SET ENRICHED FOR SCHIZOPHRENIA RISK GENES IS CHARACTERIZED BY A COMMON TRANSCRIPTIONAL REGULATION INVOLVING NURR1 TRANSCRIPTION FACTOR

Genome-wide association studies demonstrated that multiple genetic variants are associated with schizophrenia (SCZ). Additional evidence revealed that genes are prone to operate in functional molecular networks that subtend complex clinical phenotypes. This knowledge raises the need to investigate how genes linked to SCZ and their possible co-regulators are inserted into molecular networks with a key impact in disease pathogenesis. Using post-mortem brain mRNA data sets (Pergola et al. 2017), we have previously identified a co-expression network enriched for SCZ risk genes, including DRD2, the gene coding for the D2 dopamine receptor, and predicted cognitive and neuroimaging phenotypes of SCZ, as well as response to antipsychotic treatment. Given the relevance of DRD2 to the pathophysiology of SCZ, in the current study we sought to further our understanding of biological mechanisms underpinning co-expression of the DRD2 network. In detail, we aimed at probing the hypothesis that expression of genes within the DRD2-related co-expression network is modulated by a common transcriptional regulation involving one or more Transcription factors (TFs).