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Hum Mol Genet. 2017 Jan 1;26(1):210-225. doi: 10.1093/hmg/ddw373.

Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.

Author information

1
University of Exeter Medical School, University of Exeter, Exeter, UK.
2
Garvan Institute of Medical Research, Sydney, NSW, Australia.
3
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
4
Douglas Mental Health Institute, McGill University, Montreal, QC, Canada and.
5
School of Biological Sciences, University of Essex, Colchester, UK.

Abstract

Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease.

PMID:
28011714
PMCID:
PMC5351932
DOI:
10.1093/hmg/ddw373
[Indexed for MEDLINE]
Free PMC Article

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