Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia.

TitleMethylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia.
Publication TypeJournal Article
Year of Publication2014
AuthorsPidsley R, Viana J, Hannon E, Spiers H, Troakes C, Al-Saraj S, Mechawar N, Turecki G, Schalkwyk LC, Bray NJ, Mill J
JournalGenome Biol
Date Published2014
KeywordsBrain, Cerebellum, DNA Methylation, Epigenesis, Genetic, Fetal Development, Humans, Prefrontal Cortex, Schizophrenia

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances ine arly brain development. There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development.RESULTS: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci,particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples.Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that schizophrenia-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development.CONCLUSIONS: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.

Alternate JournalGenome Biol.
PubMed ID25347937
PubMed Central IDPMC4262979
Grant ListG0700089 / / Wellcome Trust / United Kingdom
MR/K013807/1 / / Medical Research Council / United Kingdom
AG036039 / AG / NIA NIH HHS / United States
MC_PC_15004 / / Medical Research Council / United Kingdom
GR082557 / / Wellcome Trust / United Kingdom
G0700089 / / Medical Research Council / United Kingdom
R01 AG036039 / AG / NIA NIH HHS / United States