Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Epigenetics. 2021 Jun;16(6):662-676. doi: 10.1080/15592294.2020.1817290. Epub 2020 Sep 30.
Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through local genotype and, quite surprisingly, found that genetic factors explained an overwhelming majority of the variation in DNAm levels at other, previously identified, environmentally-associated CpGs. These results indicate that race-associated blood DNAm patterns in particular, and blood DNAm levels in general, are primarily driven by genetic factors, and are not as sensitive to environmental exposures as previously suggested, at least during the first 7 years of life.
表观遗传结构受遗传和环境因素的影响，但人们对它们的相对贡献或纵向动态知之甚少。在这里，我们研究了主要自我报告为黑人和西班牙裔的 196 名儿童在出生时和 7 岁时采集的单核血细胞中超过 750,000 个 CpG 位点的 DNA 甲基化 (DNAm)，以研究与种族相关的 DNAm 模式。我们开发了一种新的贝叶斯方法来处理高维纵向数据，并表明出生时和 7 岁时与种族相关的 DNAm 模式几乎相同。此外，我们估计高达 51%的所有自我报告的与种族相关的 CpG 具有种族依赖性的 DNAm 水平，这些水平是通过局部基因型介导的，而且令人惊讶的是，我们发现遗传因素解释了其他先前确定的与环境相关的 CpG 中 DNAm 水平变化的绝大多数。这些结果表明，与种族相关的血液 DNAm 模式，特别是一般的血液 DNAm 水平，主要由遗传因素驱动，并且不像以前所建议的那样容易受到环境暴露的影响，至少在生命的前 7 年是这样。
