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Gene expression in patient-derived neural progenitors provide insights into neurodevelopmental aspects of schizophrenia

By Oleg V. Evgrafov, Chris Armoskus, Bozena B Wrobel, Valeria N Spitsyna, Tade Souaiaia, Jenifer S Herstein, Christopher P Walker, Joseph D Nguyen, Adrian Camarena, Jonathan R Weitz, Jae Mun 'Hugo' Kim, Edder Lopez Duarte, Kai Wang, George M Simpson, Janet L Sobell, Helena Medeiros, Michele T Pato, Carlos N Pato, James A. Knowles

Posted 26 Oct 2017
bioRxiv DOI: 10.1101/209197

The PGC2 schizophrenia (SCZ) GWAS shows that variation in non-coding regions is responsible for most of the common variation heritability of the disease, suggesting risk variants alter gene expression. Therefore, comparing differences in gene expression between cases and controls may provide a direct approach for studying the etiology of SCZ. We studied transcriptome expression profiles of Cultured Neural progenitor cells derived from Olfactory Neuroepithelium lines (CNON) from 144 SCZ and 111 control individuals using RNA-Seq and identified 53 differentially expressed (DEX) genes (FDR<0.10). Most DEX genes are implicated in Wnt or Notch signaling, or the metabolism of serine/glutamine/asparagine. DEX genes show enrichment for overlap with significant variants from the SCZ GWAS, and for GO terms related to neurodevelopment: cell differentiation, migration, neurogenesis, and synapse assembly. Our findings show the utility of gene expression analysis of neural progenitors for deciphering molecular aberrations associated with, and potentially causing, schizophrenia.

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