Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Environ Res. 2022 Nov;214(Pt 1):113881. doi: 10.1016/j.envres.2022.113881. Epub 2022 Jul 11.
Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth.
Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM) and ozone (O), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM and O in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood.
We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant.
Differentially methylated regions in cord blood were identified in association with maternal exposure to PM and O. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O exposure and 5-month infant adiposity.
产前暴露于环境空气污染与不良后代健康结果有关。产前暴露对儿童健康的影响可能通过出生时可检测到的 DNA 甲基化变化来介导。
在美国科罗拉多州的一项母婴队列研究中，我们对 429 名不吸烟的女性进行了研究，估计了产前暴露于环境细颗粒物 (PM) 和臭氧 (O) 与脐带血细胞表观基因组全基因组 DNA 甲基化之间的关联，分娩时（2010-2014 年）。我们在每个孕期和整个孕期计算了每个季度的平均 PM 和 O，使用反距离加权插值法进行计算。我们使用线性回归模型来调整潜在的混杂因素和细胞比例，以估计每种污染物与 432943 个 CpG 位点之间的关联。使用 comb-p 识别差异甲基化区域 (DMR)。在此队列中，我们之前报告了第三孕期 O 暴露与 5 个月大婴儿肥胖之间的正相关关系。在这里，我们量化了脐带血中 DNA 甲基化变化对该关联的潜在介导作用。
我们为每个污染物和孕期确定了几个 DMR。与第三孕期 PM 相关的 DMR 数量最多（21 个 DMR）。没有单个 CpG 在错误发现率 <0.05 下与空气污染物相关。我们发现，第三孕期 O 对 5 个月大婴儿肥胖的影响可能有高达 8%是由特定基因座的甲基化变化介导的，但介导估计没有统计学意义。
脐带血中的差异甲基化区域与母体 PM 和 O 暴露有关。注释到显著位点的基因在心血管代谢疾病、免疫功能和炎症以及神经紊乱中发挥作用。我们发现，第三孕期 O 暴露与 5 个月大婴儿肥胖之间的关联通过 DNA 甲基化介导的证据有限。
