Papers

International journal
May 4, 2023

Identification of schizophrenia symptom-related gene modules by postmortem brain transcriptome analysis.

Translational psychiatry
  • Kazusa Miyahara
  • ,
  • Mizuki Hino
  • ,
  • Risa Shishido
  • ,
  • Atsuko Nagaoka
  • ,
  • Ryuta Izumi
  • ,
  • Hideki Hayashi
  • ,
  • Akiyoshi Kakita
  • ,
  • Hirooki Yabe
  • ,
  • Hiroaki Tomita
  • ,
  • Yasuto Kunii

Volume
13
Number
1
First page
144
Last page
144
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1038/s41398-023-02449-8

Schizophrenia is a multifactorial disorder, the genetic architecture of which remains unclear. Although many studies have examined the etiology of schizophrenia, the gene sets that contribute to its symptoms have not been fully investigated. In this study, we aimed to identify each gene set associated with corresponding symptoms of schizophrenia using the postmortem brains of 26 patients with schizophrenia and 51 controls. We classified genes expressed in the prefrontal cortex (analyzed by RNA-seq) into several modules by weighted gene co-expression network analysis (WGCNA) and examined the correlation between module expression and clinical characteristics. In addition, we calculated the polygenic risk score (PRS) for schizophrenia from Japanese genome-wide association studies, and investigated the association between the identified gene modules and PRS to evaluate whether genetic background affected gene expression. Finally, we conducted pathway analysis and upstream analysis using Ingenuity Pathway Analysis to clarify the functions and upstream regulators of symptom-related gene modules. As a result, three gene modules generated by WGCNA were significantly correlated with clinical characteristics, and one of these showed a significant association with PRS. Genes belonging to the transcriptional module associated with PRS significantly overlapped with signaling pathways of multiple sclerosis, neuroinflammation, and opioid use, suggesting that these pathways may also be profoundly implicated in schizophrenia. Upstream analysis indicated that genes in the detected module were profoundly regulated by lipopolysaccharides and CREB. This study identified schizophrenia symptom-related gene sets and their upstream regulators, revealing aspects of the pathophysiology of schizophrenia and identifying potential therapeutic targets.

Link information
DOI
https://doi.org/10.1038/s41398-023-02449-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/37142572
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160042
ID information
  • DOI : 10.1038/s41398-023-02449-8
  • Pubmed ID : 37142572
  • Pubmed Central ID : PMC10160042

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