Patterns of methylation heritability in a genome-wide analysis of four brain regions. Nucleic acids research 41

DNA methylation has been implicated in a number of diseases and other phenotypes. It is, therefore, of interest to identify and understand the genetic deter-minants of methylation and epigenomic variation. We investigated the extent to which genetic variation in cis-DNA sequence explains variation in CpG di-nucleotide 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 tran-scription 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 herit-ability 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 herit-able loci depends on the window size parameter commonly used to identify candidate cis-acting single-nucleotide polymorphism variants