1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts, USA.
2 The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.
Environ Health Perspect. 2018 Sep;126(9):97006. doi: 10.1289/EHP2034.
Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.
We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes.
We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression.
Living closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study.
Our discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.
表观遗传变异性被假设为一种调节途径，通过这种途径，产前暴露可能会影响儿童的发育和健康。
我们试图研究出生时接近道路的居住环境与全基因组 DNA 甲基化之间的关联。我们还评估了差异甲基化与儿童认知结果之间的关联。
我们使用地理信息系统 (GIS) 来估计出生时接近道路的居住环境，并使用 Illumina 的 HumanMethylation450 阵列在 Project Viva 的 482 对母婴对中测量脐带血甲基化。我们使用稳健的线性回归 [[公式：见正文]] 来识别与出生时接近道路相关的个体 CpG。我们还估计了出生时接近道路与在 7-11 岁时采集的血液样本中相同位点的甲基化之间的关联 [[公式：见正文]]。我们在 Generation R 研究中进行了相同的分析以进行复制 [[公式：见正文]]。在 Project Viva 中，我们使用线性回归研究了出生时差异甲基化与儿童中期认知之间的关联。
出生时靠近主要道路与四个 LAMB2 基因位点的脐带血（以及更弱的儿童中期血液）甲基化水平升高有关。与主要道路的居住环境接近减半相比，我们观察到 cg05654765 处的 DNA 甲基化增加了 0.82%[95%置信区间 (CI)：(0.54%，1.10%)]，cg14099457 处增加了 0.88%[95% CI：(0.56%，1.19%)]，cg03732535 处增加了 0.19%[95% CI：(0.11%，0.28%)]，cg02954987 处增加了 1.08%[95% CI：(0.65%，1.51%)]。这些位点的脐带血甲基化水平升高与儿童中期非语言认知评分降低有关。我们的结果在 Generation R 研究中没有得到复制。
鉴于我们的发现结果在另一个队列中没有得到复制，因此必须谨慎解释。然而，在我们的美国队列中，出生时靠近主要道路与 LAMB2 基因位点的脐带血甲基化有关，该基因与轴突发育有关。在同一儿童中，这些位点的甲基化水平升高与 7-11 岁时的非语言认知评分较低有关。https://doi.org/10.1289/EHP2034.
