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Transl Psychiatry. 2014 Jan 7;4:e339. doi: 10.1038/tp.2013.111.

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients.

Author information

1
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
2
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
3
1] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia [2] Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
4
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.

Abstract

Recent studies suggest that genetic and environmental factors do not account for all the schizophrenia risk, and epigenetics also has a role in disease susceptibility. DNA methylation is a heritable epigenetic modification that can regulate gene expression. Genome-wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485,000 CpG sites using the Illumina Infinium HumanMethylation450 Bead Chip. After adjusting for age and post-mortem interval, 4641 probes corresponding to 2929 unique genes were found to be differentially methylated. Of those genes, 1291 were located in a CpG island and 817 were in a promoter region. These include NOS1, AKT1, DTNBP1, DNMT1, PPP3CC and SOX10, which have previously been associated with schizophrenia. More than 100 of these genes overlap with a previous DNA methylation study of peripheral blood from schizophrenia patients in which 27,000 CpG sites were analysed. Unsupervised clustering analysis of the top 3000 most variable probes revealed two distinct groups with significantly more people with schizophrenia in cluster one compared with controls (P=1.74 × 10(-4)). The first cluster composed of 88% of patients with schizophrenia and only 12% controls, whereas the second cluster composed of 27% of patients with schizophrenia and 73% controls. These results strongly suggest that differential DNA methylation is important in schizophrenia etiology and add support for the use of DNA methylation profiles as a future prognostic indicator of schizophrenia.

PMID:
24399042
PMCID:
PMC3905221
DOI:
10.1038/tp.2013.111
[Indexed for MEDLINE]
Free PMC Article

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