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Population-specificity of human DNA methylation.


ABSTRACT: Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are largely unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated.Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities also differ between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that most of the population specificity can be explained by divergence in allele frequencies between populations, and that there is little overlap in genetic associations between populations. These population-specific genetic associations are supported by the patterns of DNA methylation in several hundred brain samples, suggesting that they hold in vivo and across tissues.These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to a combination of differences in allele frequencies and complex epistasis or gene × environment interactions.

SUBMITTER: Fraser HB 

PROVIDER: S-EPMC3334571 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Population-specificity of human DNA methylation.

Fraser Hunter B HB   Lam Lucia L LL   Neumann Sarah M SM   Kobor Michael S MS  

Genome biology 20120209 2


<h4>Background</h4>Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are largely unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated.<h4>Results</h4>Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population. We find popula  ...[more]

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