Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620272
Title:
Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.
Authors:
Hannon, E.; Spiers, H.; Viana, J.; Pidsley, R.; Burrage, J.; Murphy, T. M.; Troakes, C.; Turecki, G.; O'Donovan, M. C.; Schalkwyk, L. C.; Bray, N. J.; Mill, Jonathan
Abstract:
We characterized DNA methylation quantitative trait loci (mQTLs) in a large collection (n = 166) of human fetal brain samples spanning 56-166 d post-conception, identifying >16,000 fetal brain mQTLs. Fetal brain mQTLs were primarily cis-acting, enriched in regulatory chromatin domains and transcription factor binding sites, and showed substantial overlap with genetic variants that were also associated with gene expression in the brain. Using tissue from three distinct regions of the adult brain (prefrontal cortex, striatum and cerebellum), we found that most fetal brain mQTLs were developmentally stable, although a subset was characterized by fetal-specific effects. Fetal brain mQTLs were enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia, a severe psychiatric disorder with a hypothesized neurodevelopmental component. Finally, we found that mQTLs can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with schizophrenia risk variants.
Citation:
Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. 2016, 19 (1):48-54 Nat. Neurosci.
Publisher:
Nature
Journal:
Nature neuroscience
Issue Date:
Jan-2016
URI:
http://hdl.handle.net/11287/620272
DOI:
10.1038/nn.4182
PubMed ID:
26619357
Additional Links:
http://dx.doi.org/10.1038/nn.4182
Type:
Journal Article
Language:
en
ISSN:
1546-1726
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHannon, E.en
dc.contributor.authorSpiers, H.en
dc.contributor.authorViana, J.en
dc.contributor.authorPidsley, R.en
dc.contributor.authorBurrage, J.en
dc.contributor.authorMurphy, T. M.en
dc.contributor.authorTroakes, C.en
dc.contributor.authorTurecki, G.en
dc.contributor.authorO'Donovan, M. C.en
dc.contributor.authorSchalkwyk, L. C.en
dc.contributor.authorBray, N. J.en
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2017-03-13T10:12:46Z-
dc.date.available2017-03-13T10:12:46Z-
dc.date.issued2016-01-
dc.identifier.citationMethylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. 2016, 19 (1):48-54 Nat. Neurosci.en
dc.identifier.issn1546-1726-
dc.identifier.pmid26619357-
dc.identifier.doi10.1038/nn.4182-
dc.identifier.urihttp://hdl.handle.net/11287/620272-
dc.description.abstractWe characterized DNA methylation quantitative trait loci (mQTLs) in a large collection (n = 166) of human fetal brain samples spanning 56-166 d post-conception, identifying >16,000 fetal brain mQTLs. Fetal brain mQTLs were primarily cis-acting, enriched in regulatory chromatin domains and transcription factor binding sites, and showed substantial overlap with genetic variants that were also associated with gene expression in the brain. Using tissue from three distinct regions of the adult brain (prefrontal cortex, striatum and cerebellum), we found that most fetal brain mQTLs were developmentally stable, although a subset was characterized by fetal-specific effects. Fetal brain mQTLs were enriched amongst risk loci identified in a recent large-scale genome-wide association study (GWAS) of schizophrenia, a severe psychiatric disorder with a hypothesized neurodevelopmental component. Finally, we found that mQTLs can be used to refine GWAS loci through the identification of discrete sites of variable fetal brain methylation associated with schizophrenia risk variants.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/nn.4182en
dc.rightsArchived with thanks to Nature neuroscienceen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleMethylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.en
dc.typeJournal Articleen
dc.identifier.journalNature neuroscienceen
dc.type.versionPublisheden

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