Prefrontal co-expression of schizophrenia risk genes is associated with treatment response in patients

Abstract Background Gene co-expression networks are relevant to functional and clinical translation of schizophrenia risk genes. We hypothesized that schizophrenia risk genes converge into co-expression pathways which may be associated with gene regulation mechanisms and with response to treatment in patients with schizophrenia. Methods We identified gene co-expression networks in two prefrontal cortex post-mortem RNA sequencing datasets (N=688) and replicated them in four more datasets (N=1295). We identified and replicated (p-values In silico screening of potential regulators of the schizophrenia risk module via bioinformatic analyses identified two transcription factors and three miRNAs associated with the risk module. To translate post-mortem information into clinical phenotypes, we identified polymorphisms predicting co-expression and combined them to obtain an index approximating module co-expression (Polygenic Co-expression Index: PCI). Results The PCI-co-expression association was successfully replicated in two independent brain transcriptome datasets (N=131; p-values Conclusions In summary, our findings in 1983 samples of human post-mortem prefrontal cortex show that co-expression of a set of genes enriched for schizophrenia risk genes is relevant to treatment response. This co-expression pathway may be co-regulated by transcription factors and miRNA associated with it.