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Published VersionCC BY V3.0, Open Access
Journal article
Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients
Translational Psychiatry, Vol.4(1), pp.1-8
2014
PMCID: PMC3905221
PMID: 24399042
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.
Details
- Title
- Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients
- Authors
- L F Wockner (Author) - QIMR Berghofer Medical Research InstituteErnest P Noble (Author) - University of California Los AngelesB R Lawford (Author) - Queensland University of TechnologyRoss Young (Author) - Queensland University of TechnologyC P Morris (Author) - Queensland University of TechnologyV L J Whitehall (Author) - QIMR Berghofer Medical Research InstituteJ Voisey (Author) - Queensland University of Technology
- Publication details
- Translational Psychiatry, Vol.4(1), pp.1-8
- Publisher
- Nature Publishing Group
- Date published
- 2014
- DOI
- 10.1038/tp.2013.111
- ISSN
- 2158-3188
- PMID
- 24399042; PMC3905221
- Copyright note
- © 2014 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of the Deputy Vice-Chancellor (Research and Innovation)
- Language
- English
- Record Identifier
- 99550996402621
- Output Type
- Journal article
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