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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620191
Title:
Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions
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, Jonathan
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.
Citation:
Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions 2017 26 (1): 210-225 Epub Dec 22 Human Molecular Genetics
Publisher:
Oxford Journals
Journal:
Human Molecular Genetics
Issue Date:
22-Dec-2016
URI:
http://hdl.handle.net/11287/620191
DOI:
10.1093/hmg/ddw373
Additional Links:
http://hmg.oxfordjournals.org/lookup/doi/10.1093/hmg/ddw373
Type:
Journal Article
Language:
en
ISSN:
0964-6906; 1460-2083
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorViana, J.en
dc.contributor.authorHannon, E.en
dc.contributor.authorDempster, E.en
dc.contributor.authorPidsley, R.en
dc.contributor.authorMacdonald, R.en
dc.contributor.authorKnox, O.en
dc.contributor.authorSpiers, H.en
dc.contributor.authorTroakes, C.en
dc.contributor.authorAl-Saraj, S.en
dc.contributor.authorTurecki, G.en
dc.contributor.authorSchalkwyk, L. C.en
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2017-01-19T11:38:54Z-
dc.date.available2017-01-19T11:38:54Z-
dc.date.issued2016-12-22-
dc.identifier.citationSchizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions 2017 26 (1): 210-225 Epub Dec 22 Human Molecular Geneticsen
dc.identifier.issn0964-6906-
dc.identifier.issn1460-2083-
dc.identifier.doi10.1093/hmg/ddw373-
dc.identifier.urihttp://hdl.handle.net/11287/620191-
dc.description.abstractGenetic 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.en
dc.language.isoenen
dc.publisherOxford Journalsen
dc.relation.urlhttp://hmg.oxfordjournals.org/lookup/doi/10.1093/hmg/ddw373en
dc.rightsArchived with thanks to Human Molecular Geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Psychologyen
dc.titleSchizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regionsen
dc.typeJournal Articleen
dc.identifier.journalHuman Molecular Geneticsen
dc.type.versionIn press (epub ahead of print)en
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