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Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia

Pidsley, Ruth, Viana, Joana, Hannon, Eilis, Spiers, Helen, Troakes, Claire, Al-Saraj, Safa, Mechawar, Naguib, Turecki, Gustavo, Schalkwyk, Leonard C., Bray, Nicholas John and Mill, Jonathan 2014. Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia. Genome Biology 15 (10) , 483. 10.1186/s13059-014-0483-2

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Abstract

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances ine arly brain development. There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. RESULTS: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci,particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples.Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that schizophrenia-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. CONCLUSIONS: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. Comment in Crucial timing in schizophrenia: role of DNA methylation in early neurodevelopment. [Genome Biol. 2014]

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Publisher: BioMed Central
ISSN: 1465-6906
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 24 September 2014
Last Modified: 07 Feb 2019 11:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/82232

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