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

Hannon, Eilis, Spiers, Helen, Viana, Joana, Pidsley, Ruth, Burrage, Joe, Murphy, Therese M., Troakes, Claire, Turecki, Gustavo, O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379, Schalkwyk, Leonard C., Bray, Nicholas J. ORCID: https://orcid.org/0000-0002-4357-574X and Mill, Jonathan 2016. Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nature Neuroscience 19 (1) , pp. 48-54. 10.1038/nn.4182

Preview

PDF - Accepted Post-Print Version Download (230kB) | Preview

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
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Nature Publishing Group
ISSN:	1097-6256
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	30 October 2015
Last Modified:	16 Nov 2024 03:45
URI:	https://orca.cardiff.ac.uk/id/eprint/84363

Citation Data

Cited 213 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item