Publications

Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

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

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.

Type Journal
ISBN 1460-2083 (Electronic) 0964-6906 (Linking)
Authors Viana, J.; Hannon, E.; Dempster, E.; Pidsley, R.; Macdonald, R.; Knox, O.; Spiers, H.; Troakes, C.; Al-Saraj, S.; Turecki, G.; Schalkwyk, L. C.; Mill, J.
Responsible Garvan Author Dr Ruth Pidsley
Publisher Name HUMAN MOLECULAR GENETICS
Published Date 2017-01-31 00:00:00
Published Volume 26
Published Issue 1
Published Pages 210-225
Status Published in-print
DOI 10.1093/hmg/ddw373
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28011714
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/14413