Transcriptome study of differential expression in schizophrenia

Sanders, Alan R., Goering, Harald H. H., Duan, Jubao, Drigalenko, Eugene I., Moy, Winton, Freda, Jessica, He, Deli, Shi, Jianxin, Gejman, Pablo V., Molecular Genetics of Schizophrenia (MGS) and Mowry, Bryan (2013) Transcriptome study of differential expression in schizophrenia. Human Molecular Genetics, 22 24: 5001-5014. doi:10.1093/hmg/ddt350


Author Sanders, Alan R.
Goering, Harald H. H.
Duan, Jubao
Drigalenko, Eugene I.
Moy, Winton
Freda, Jessica
He, Deli
Shi, Jianxin
Gejman, Pablo V.
Molecular Genetics of Schizophrenia (MGS)
Mowry, Bryan
Title Transcriptome study of differential expression in schizophrenia
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2013-12-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddt350
Open Access Status Not yet assessed
Volume 22
Issue 24
Start page 5001
End page 5014
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract Schizophrenia genome-wide association studies (GWAS) have identified common SNPs, rare copy number variants (CNVs) and a large polygenic contribution to illness risk, but biological mechanisms remain unclear. Bioinformatic analyses of significantly associated genetic variants point to a large role for regulatory variants. To identify gene expression abnormalities in schizophrenia, we generated whole-genome gene expression profiles using microarrays on lymphoblastoid cell lines (LCLs) from 413 cases and 446 controls. Regression analysis identified 95 transcripts differentially expressed by affection status at a genome-wide false discovery rate (FDR) of 0.05, while simultaneously controlling for confounding effects. These transcripts represented 89 genes with functions such as neurotransmission, gene regulation, cell cycle progression, differentiation, apoptosis, microRNA (miRNA) processing and immunity. This functional diversity is consistent with schizophrenia's likely significant pathophysiological heterogeneity. The overall enrichment of immune-related genes among those differentially expressed by affection status is consistent with hypothesized immune contributions to schizophrenia risk. The observed differential expression of extended major histocompatibility complex (xMHC) region histones (HIST1H2BD, HIST1H2BC, HIST1H2BH, HIST1H2BG and HIST1H4K) converges with the genetic evidence from GWAS, which find the xMHC to be the most significant susceptibility locus. Among the differentially expressed immune-related genes, B3GNT2 is implicated in autoimmune disorders previously tied to schizophrenia risk (rheumatoid arthritis and Graves' disease), and DICER1 is pivotal in miRNA processing potentially linking to miRNA alterations in schizophrenia (e.g. MIR137, the second strongest GWAS finding). Our analysis provides novel candidate genes for further study to assess their potential contribution to schizophrenia.
Keyword Gene expression
Genome
Histones
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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