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

Viana, J and Hannon, E and Dempster, E and Pidsley, R and Macdonald, R and Knox, O and Spiers, H and Troakes, C and Al-Saraj, S and Turecki, G and Schalkwyk, LC and Mill, J (2017) 'Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.' Human molecular genetics, 26 (1). 210 - 225. ISSN 1460-2083

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Abstract

© The Author 2016. Published by Oxford University Press. 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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Leonard Schalkwyk
Date Deposited: 23 Jan 2017 14:45
Last Modified: 16 Oct 2017 13:15
URI: http://repository.essex.ac.uk/id/eprint/18799

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