Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures
Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures
复制标题
DOI：
10.7554/elife.20532
复制
发表时间：
2017-01-03
期刊：
影响因子：
7.7
通讯作者：
Zaitlen, Noah
中科院分区：
文献类型：
--
作者：
Galanter, Joshua M.;Gignoux, Christopher R.;Zaitlen, Noah
人口通常根据社会结构而不是生物学结构被分类为不同的种族/族裔群体。遗传祖先被认为是这种分类的另一种选择。在此，我们对573名不同西班牙裔个体的全血中超过450,000个CpG位点进行了分型，这些个体也具有高密度的基因型数据。我们发现，自我识别的种族和遗传决定的祖先分别与916和194 CpGs的甲基化水平显著相关，共同的基因组祖先占与种族相关的甲基化差异的中位数为75.7% （IQR为45.8%至92%）。在先前与环境暴露相关的位点中，特别是孕妇在怀孕期间吸烟，与种族相关的位点显著增加（p=4.2X10(-64)）。我们得出的结论是，不同种族之间甲基化的差异部分可以用共同的遗传祖先来解释，但祖先未捕获的环境因素对甲基化的差异有显著影响。
Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2X10(-64)) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation.