DLPFC Transcriptome Defines Two Molecular Subtypes of Schizophrenia

Abstract

The Clinical Brain Disorders Branch of the Intramural Research Program at the National Institutes of Health assembled a large collection of frozen post-mortem human brains from individuals diagnosed with schizophrenia and other psychiatric diagnoses, as well as matched control individuals. Illumina HumanHT-12 v4 expression array data was collected from dorsolateral prefrontal cortex (DLPFC) and the data deposited at dbGaP (Study ID: phs000979). We report an analysis of the data from the 189 adult schizophrenics and 206 adult controls in that cohort.\n\nTranscripts from 633 genes are differentially expressed in the DLPFC of schizophrenics as compared to the controls at levels of statistical significance which survive Bonferroni correction. Seventeen of those genes are differentially expressed at a level of statistical significance less than 10-8 after Bonferroni correction.\n\nWeighted Gene Co-expression Network Analysis (WGCNA) of the schizophrenic subjects using differentially expressed gene module eigengenes divides them into two groups, \"type 1\" and \"type 2.\" There are 2,635 genes differentially expressed in the DLPFC of type 2 schizophrenics at a level of statistical significance which survives Bonferroni correction. Of them 221 have P-values less than 10-15 after Bonferroni correction. In the type 1 schizophrenics however, only 6 genes are differentially expressed in the DLPFC at a level of statistical significance which survives Bonferroni correction. This striking difference in their DLPFC transcriptomes emphasizes the fundamental biologic difference between these two groups of patients.