Department of Biology, Stanford University, Stanford, CA 94305, USA.
Genome Biol. 2012 Feb 9;13(2):R8. doi: 10.1186/gb-2012-13-2-r8.
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.
已经有许多 CpG 位点证明了人类 DNA 甲基化存在种族差异，但这些差异的全基因组模式和程度在很大程度上尚不清楚。此外，多态性 DNA 甲基化的遗传控制是否具有种群特异性尚未得到研究。
在这里，我们测量了来自一个非洲人和一个欧洲人群的 180 个细胞系中超过 14000 个基因的转录起始位点附近的 DNA 甲基化。我们发现，超过三分之一的基因存在种群特异性的 DNA 甲基化模式。此外，尽管超过 1000 个 CpG 位点的甲基化具有遗传性，但这些遗传性在不同人群之间也存在差异，这表明 DNA 甲基化的遗传控制存在广泛的分歧。支持这一观点的是，DNA 甲基化的遗传图谱表明，大多数种群特异性可以通过种群之间等位基因频率的差异来解释，并且种群之间的遗传关联几乎没有重叠。这些种群特异性的遗传关联得到了数百个脑组织样本中 DNA 甲基化模式的支持，表明它们在体内和跨组织中存在。
这些结果表明，DNA 甲基化在不同人群之间存在高度差异，这种差异可能在很大程度上是由于等位基因频率的差异以及复杂的上位性或基因×环境相互作用的综合作用。
