title: Expression analysis of the genes identified in GWAS of the postmortem brain tissues from patients with schizophrenia.
abstract: Many gene expression studies have examined postmortem brain tissues of patients with schizophrenia. However, only a few expression studies of the genes identified in genome-wide association study (GWAS) have been published to date. We measured the expression levels of the genes identified in GWAS (ZNF804A, OPCML, RPGRIP1L, NRGN, and TCF4) of the postmortem brain tissues of patients with schizophrenia and controls from two separate sample sets (i.e., the Australian Tissue Resource Center and Stanley Medical Research Institute). We also determined whether the single-nucleotide polymorphisms (SNPs) identified in the GWAS were related to the gene expression changes in the prefrontal cortex. No difference was observed between the patients with schizophrenia and controls from the Australian Tissue Resource Center samples in the mRNA levels of ZNF804A, OPCML, RPGRIP1L, NRGN, or TCF4. The lack of mRNA change for these five transcripts was also found in the brain samples from the Stanley Medical Research Institute. In addition, no relationship between the schizophrenia-associated SNPs identified in the GWAS and the corresponding gene expression was observed in either sample set. Our results suggest that major changes in the transcript levels of the five candidate genes identified in the GWAS may not occur in adult patients with schizophrenia. The lack of linkage between the risk gene polymorphisms and the expression levels of their major transcripts suggests that the control of pan mRNA levels may not be a prominent mechanism by which the genes identified in the GWAS contribute to the pathophysiology of schizophrenia. Further studies are needed to examine how the genes identified in the GWAS contribute to the pathophysiology of schizophrenia.
authors.affiliation: Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Umeda-Yano
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka 5650871, Japan. Electronic address: hashimor@psy.med.osaka-u.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Schizophrenia Research Institute, Darlinghurst, NSW 2010, Australia; Neuroscience Research Australia, Barker St, Randwick, NSW 2031, Australia; School of Psychiatry, University of New South Wales, Randwick, NSW 2031, Australia.
authors.forename: Cynthia Shannon
authors.initials: CS
authors.lastname: Weickert
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 5650871, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051579:Neurogranin / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D051741:Kruppel-Like Transcription Factors; C496649:NRGN protein, human; C059785:OPCML protein, human; D012333:RNA, Messenger; C532826:RPGRIP1L protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C540527:ZNF804A protein, human; D051579:Neurogranin
keywords: Genome-wide association study (GWAS); Postmortem brain; Schizophrenia