Patterns of methylation heritability in a genome-wide analysis of four brain regions

DNA methylation has been implicated in a number of diseases and other phenotypes. It is, therefore, of interest to identify and understand the genetic determinants of methylation and epigenomic variation. We investigated the extent to which genetic variation in cis-DNA sequence explains variation in...

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Main Authors:	Quon, Gerald, Lippert, Christoph, Heckerman, David, Listgarten, Jennifer
Format:	Online
Language:	English
Published:	Oxford University Press 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575819/

id	pubmed-3575819
recordtype	oai_dc
spelling	pubmed-35758192013-02-19 Patterns of methylation heritability in a genome-wide analysis of four brain regions Quon, Gerald Lippert, Christoph Heckerman, David Listgarten, Jennifer Computational Biology DNA methylation has been implicated in a number of diseases and other phenotypes. It is, therefore, of interest to identify and understand the genetic determinants of methylation and epigenomic variation. We investigated the extent to which genetic variation in cis-DNA sequence explains variation in CpG dinucleotide methylation in publicly available data for four brain regions from unrelated individuals, finding that 3–4% of CpG loci assayed were heritable, with a mean estimated narrow-sense heritability of 30% over the heritable loci. Over all loci, the mean estimated heritability was 3%, as compared with a recent twin-based study reporting 18%. Heritable loci were enriched for open chromatin regions and binding sites of CTCF, an influential regulator of transcription and chromatin architecture. Additionally, heritable loci were proximal to genes enriched in several known pathways, suggesting a possible functional role for these loci. Our estimates of heritability are conservative, and we suspect that the number of identified heritable loci will increase as the methylome is assayed across a broader range of cell types and the density of the tested loci is increased. Finally, we show that the number of heritable loci depends on the window size parameter commonly used to identify candidate cis-acting single-nucleotide polymorphism variants. Oxford University Press 2013-02 2013-01-07 /pmc/articles/PMC3575819/ /pubmed/23303775 http://dx.doi.org/10.1093/nar/gks1449 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Quon, Gerald Lippert, Christoph Heckerman, David Listgarten, Jennifer
spellingShingle	Quon, Gerald Lippert, Christoph Heckerman, David Listgarten, Jennifer Patterns of methylation heritability in a genome-wide analysis of four brain regions
author_facet	Quon, Gerald Lippert, Christoph Heckerman, David Listgarten, Jennifer
author_sort	Quon, Gerald
title	Patterns of methylation heritability in a genome-wide analysis of four brain regions
title_short	Patterns of methylation heritability in a genome-wide analysis of four brain regions
title_full	Patterns of methylation heritability in a genome-wide analysis of four brain regions
title_fullStr	Patterns of methylation heritability in a genome-wide analysis of four brain regions
title_full_unstemmed	Patterns of methylation heritability in a genome-wide analysis of four brain regions
title_sort	patterns of methylation heritability in a genome-wide analysis of four brain regions
description	DNA methylation has been implicated in a number of diseases and other phenotypes. It is, therefore, of interest to identify and understand the genetic determinants of methylation and epigenomic variation. We investigated the extent to which genetic variation in cis-DNA sequence explains variation in CpG dinucleotide methylation in publicly available data for four brain regions from unrelated individuals, finding that 3–4% of CpG loci assayed were heritable, with a mean estimated narrow-sense heritability of 30% over the heritable loci. Over all loci, the mean estimated heritability was 3%, as compared with a recent twin-based study reporting 18%. Heritable loci were enriched for open chromatin regions and binding sites of CTCF, an influential regulator of transcription and chromatin architecture. Additionally, heritable loci were proximal to genes enriched in several known pathways, suggesting a possible functional role for these loci. Our estimates of heritability are conservative, and we suspect that the number of identified heritable loci will increase as the methylome is assayed across a broader range of cell types and the density of the tested loci is increased. Finally, we show that the number of heritable loci depends on the window size parameter commonly used to identify candidate cis-acting single-nucleotide polymorphism variants.
publisher	Oxford University Press
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575819/
_version_	1611955950941372416

Patterns of methylation heritability in a genome-wide analysis of four brain regions

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