Patterns of methylation heritability in a genome-wide analysis of four brain regions
Name
Quon-2013-Patterns of methylation heritability in a genome-wide analysis of four brain regions.pdf
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1.06 MB
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Adobe PDF
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Author(s)
Quon, Gerald
Lippert, Christoph
Heckerman, David
Listgarten, Jennifer
Date Issued
January 2013
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Citation
Quon, G. et al. “Patterns of Methylation Heritability in a Genome-wide Analysis of Four Brain Regions.” Nucleic Acids Research 41.4 (2013): 2095–2104.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
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Creative Commons Attribution 3.0
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DOI of Published Version
https://doi.org/10.1093/nar/gks1449
