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Schizophr Res. 2015 Dec;169(1-3):447-452. doi: 10.1016/j.schres.2015.08.035. Epub 2015 Sep 14.

The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients.

Author information

1
The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA. Electronic address: jliu@mrn.org.
2
The Mind Research Network, Albuquerque, NM, USA.
3
Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany; MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
4
Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany.
5
The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.

Abstract

Both methylation and brain volume patterns hold important biological information for the development and prognosis of schizophrenia (SZ). A combined study to probe the association between them provides a new perspective to understanding SZ. Genomic methylation of peripheral blood and regional brain volumes derived from magnetic resonance imaging were analyzed using parallel independent component analyses in this study. Nine methylation components and five brain volumetric components were extracted for 94 SZ patients and 106 healthy controls. After controlling for age, sex, race, and substance use, a component comprised primarily of bilateral cerebellar volumes was significantly correlated to a methylation component from 14 CpG sites in 13 genes. Both patients and healthy controls demonstrated similar associations, but patients had significantly smaller cerebellar volumes and dysmethylation in the associated epigenetic component compared to controls. The 13 genes are enriched in cellular growth and proliferation with some genes involved in neuronal growth and cerebellum development (GATA4, ADRA1D, EPHA3, and KCNK10), and these genes are prominently associated with neurological and psychological disorders. Such findings suggest that the methylation pattern of the genes coding for cellular growth may influence the cerebellar development through regulating gene expression, and the alteration in the methylation of these genes in SZ patients may contribute to the cerebellar volume reduction observed in patients.

KEYWORDS:

Brain volume; Cerebellum; DNA methylation; Multivariate association; Schizophrenia

PMID:
26381449
PMCID:
PMC4681600
DOI:
10.1016/j.schres.2015.08.035
[Indexed for MEDLINE]
Free PMC Article

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