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

Jingyu Liu, Peter Siyahhan Julnes, Jiayu Chen, Stefan Ehrlich, Esther Walton, Vince Daniel Calhoun

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalSchizophrenia Research
DOIs
StateAccepted/In press - Jan 26 2015
Externally publishedYes

Fingerprint

DNA Methylation
Methylation
Schizophrenia
Brain
Genes
Growth
Nervous System Diseases
Growth and Development
Epigenomics
Cerebellum
Magnetic Resonance Imaging
Cell Proliferation
Psychology
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients. / Liu, Jingyu; Siyahhan Julnes, Peter; Chen, Jiayu; Ehrlich, Stefan; Walton, Esther; Calhoun, Vince Daniel.

In: Schizophrenia Research, 26.01.2015.

Research output: Contribution to journalArticle

Liu, Jingyu ; Siyahhan Julnes, Peter ; Chen, Jiayu ; Ehrlich, Stefan ; Walton, Esther ; Calhoun, Vince Daniel. / The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients. In: Schizophrenia Research. 2015.
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