Commonality in dysregulated expression of gene sets in cortical brains of individuals with autism, schizophrenia, and bipolar disorder

Abstract

Individuals affected with different neuropsychiatric disorders such as autism (AUT), schizophrenia (SCZ) and bipolar disorder (BPD), may share similar clinical manifestations, suggesting shared genetic influences and common biological mechanisms underlying these disorders. Using brain transcriptome data gathered from postmortem donors affected with AUT, SCZ and BPD, it is now possible to identify shared dysregulated gene sets, i.e., those abnormally expressed in brains of neuropsychiatric patients, compared to non-psychiatric controls. Here, we apply a novel aberrant gene expression analysis method, coupled with consensus co-expression network analysis, to identify gene sets with shared dysregulated expression in cortical brains of individuals affected with AUT, SCZ and BPD. We identify eight gene sets with dysregulated expression shared by AUT, SCZ and BPD, 23 by AUT and SCZ, four by AUT and BPD, and two by SCZ and BPD. The identified genes are enriched with functions relevant to amino acid transport, synapse, neurotransmitter release, oxidative stress, nitric oxide synthase biosynthesis, immune response, protein folding, lysophosphatidic acid-mediated signaling and glycolysis. Our method has been proven to be effective in discovering and revealing multigene sets with dysregulated expression shared by different neuropsychiatric disorders. Our findings provide new insights into the common molecular mechanisms underlying the pathogenesis and progression of AUT, SCZ and BPD, contributing to the study of etiological overlap between these neuropsychiatric disorders.