Expression analysis of the genes identified in GWAS of the postmortem brain tissues from patients with schizophrenia.

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.