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. DOI https://doi.org/10.1038/nn.4182
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. DOI https://doi.org/10.1038/nn.4182
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. DOI https://doi.org/10.1038/nn.4182
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: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 04 Dec 2015 00:08 |
Last Modified: | 30 Oct 2024 16:09 |
URI: | http://repository.essex.ac.uk/id/eprint/15589 |
Available files
Filename: NN-A52734A%20REVISED.pdf