Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes

Sci Rep. 2020 Jan 20;10(1):630. doi: 10.1038/s41598-020-57467-z.

Abstract

Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 3 / genetics
  • Early Growth Response Protein 3 / metabolism
  • Female
  • Fibroblasts*
  • Gene Expression Profiling / methods*
  • Gene Expression*
  • Gene Regulatory Networks / genetics*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / genetics*
  • Schizophrenia / genetics*
  • Sweden
  • Synaptic Transmission / genetics*
  • Whole Exome Sequencing

Substances

  • EGR1 protein, human
  • EGR3 protein, human
  • Early Growth Response Protein 1
  • HGF protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • PRRT2 protein, human
  • Early Growth Response Protein 3
  • Hepatocyte Growth Factor