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

Hannon, Eilis and Spiers, Helen and Viana, Joana and Pidsley, Ruth and Burrage, Joe and Murphy, Therese M and Troakes, Claire and Turecki, Gustavo and O'Donovan, Michael C and Schalkwyk, Leonard C and Bray, Nicholas J and Mill, Jonathan (2016) 'Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.' Nature Neuroscience, 19 (1). pp. 48-54. ISSN 1097-6256

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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.

Item Type: Article
Uncontrolled Keywords: Brain; Cerebellum; Neostriatum; Prefrontal Cortex; Fetus; Humans; Genetic Predisposition to Disease; Risk; Gene Expression Profiling; Schizophrenia; DNA Methylation; Gene Expression; Gene Expression Regulation; Epigenesis, Genetic; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Adult; Tissue Banks; Female; Male; Genome-Wide Association Study; Genotyping Techniques
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RA Public aspects of medicine > RA790 Mental Health
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Dec 2015 00:08
Last Modified: 15 Jan 2022 00:41
URI: http://repository.essex.ac.uk/id/eprint/15589

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