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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2095-2104 |
| Number of pages | 10 |
| Journal | Nucleic Acids Research |
| Volume | 41 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 1 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
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Patterns of methylation heritability in a genome-wide analysis of four brain regions. / Quon, Gerald; Lippert, Christoph; Heckerman, David; Listgarten, Jennifer.
In: Nucleic Acids Research, Vol. 41, No. 4, 01.02.2013, p. 2095-2104.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Patterns of methylation heritability in a genome-wide analysis of four brain regions
AU - Quon, Gerald
AU - Lippert, Christoph
AU - Heckerman, David
AU - Listgarten, Jennifer
PY - 2013/2/1
Y1 - 2013/2/1
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gks1449
DO - 10.1093/nar/gks1449
M3 - Article
C2 - 23303775
AN - SCOPUS:84876394432
VL - 41
SP - 2095
EP - 2104
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 4
ER -