Differential gene expression study in whole blood identifies candidate genes for psychosis in African American individuals

Abstract

Genome-wide association has identified regions of the genome that mediate risk for psychosis. It is possible that variants in these regions confer risk by altering gene expression. This work has predominantly been conducted in individuals of European descent and has focused narrowly on schizophrenia rather than psychosis as a syndrome. In the present study we investigated alterations in gene expression in African American individuals with a range of psychotic diagnoses to increase understanding of the etiology in an underserved population.

We performed RNA-seq in whole bloody to survey the transcriptome in 126 patients with a psychosis-spectrum disorder and 217 healthy controls and applied differential gene expression analyses across the genome while controlling for age, sex, population stratification and batch. We found 18 differentially expressed genes (DEGs), some of the locations of the corresponding genes overlap with previously implicated regions for psychosis, but many of which were novel associations. Enrichment analysis of nominally significant genes (p < 0.05) revealed overrepresentation of biological processes relating to platelet, immune and cellular function, and sensory perception. Weighted gene co-expression network analysis, applied to identify modules of co-expressed genes associated with psychosis, revealed 10 modules, one of which was significantly associated with psychosis. This module was significantly enriched for DEGs, and for platelet function. These results support the potential role of immune function in the etiology of psychosis, identify novel candidate gene expression phenotypes that correspond to both established and new genomic regions, in individuals of African American ancestry.