title: The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients.
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.
authors.affiliation: 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.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Siyahhan Julnes
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Walton
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
keywords: Brain volume; Cerebellum; DNA methylation; Multivariate association; Schizophrenia