RT Journal Article
SR Electronic
T1 Gene expression in patient-derived neural progenitors implicates WNT5A signaling in the etiology of schizophrenia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 209197
DO 10.1101/209197
A1 Oleg V Evgrafov
A1 Chris Armoskus
A1 Bozena B Wrobel
A1 Valeria N Spitsyna
A1 Tade Souaiaia
A1 Jennifer S. Herstein
A1 Christopher P Walker
A1 Joseph D Nguyen
A1 Adrian Camarena
A1 Jonathan R Weitz
A1 Jae Mun ‘Hugo’ Kim
A1 Edder Lopez Duarte
A1 Kai Wang
A1 George M Simpson
A1 Janet L Sobell
A1 Helena Medeiros
A1 Michele T Pato
A1 Carlos N Pato
A1 James A Knowles
YR 2019
UL http://biorxiv.org/content/early/2019/11/04/209197.abstract
AB BACKGROUND GWAS of schizophrenia demonstrated that variations in the non-coding regions are responsible for most of common variation heritability of the disease. It is hypothesized that these risk variants alter gene expression. Thus, studying alterations in gene expression in schizophrenia may provide a direct approach to understanding the etiology of the disease. In this study we use Cultured Neural progenitor cells derived from Olfactory Neuroepithelium (CNON) as a genetically unaltered cellular model to elucidate the neurodevelopmental aspects of schizophrenia.METHODS We performed a gene expression study using RNA-Seq of CNON from 111 controls and 144 individuals with schizophrenia. Differentially expressed (DEX) genes were identified with DESeq2, using covariates to correct for sex, age, library batches and one surrogate variable component.RESULTS 80 genes were DEX (FDR<10%), showing enrichment in cell migration, cell adhesion, developmental process, synapse assembly, cell proliferation and related gene ontology categories. Cadherin and Wnt signaling pathways were positive in overrepresentation test, and, in addition, many genes are specifically involved in Wnt5A signaling. The DEX genes were significantly, enriched in the genes overlapping SNPs with genome-wide significant association from the PGC GWAS of schizophrenia (PGC SCZ2). We also found substantial overlap with genes associated with other psychiatric disorders or brain development, enrichment in the same GO categories as genes with mutations de novo in schizophrenia, and studies of iPSC-derived neural progenitor cells.CONCLUSIONS CNON cells are a good model of the neurodevelopmental aspects of schizophrenia and can be used to elucidate the etiology of the disorder.