Population-specificity of human DNA methylation.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Biology, Stanford University, Stanford, CA 94305, USA. hbfraser@stanford.edu
Hunter B
HB
Fraser
Lucia L
LL
Lam
Sarah M
SM
Neumann
Michael S
MS
Kobor
D044383:Black People / Q000235:genetics; D002460:Cell Line; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D024363:Transcription Initiation Site; D044465:White People / Q000235:genetics