Friedman Chloe, Niemiec Sierra, Dabelea Dana, Kechris Katerina, Yang Ivana V, Adgate John L, Glueck Deborah H, Martenies Sheena E, Magzamen Sheryl, Starling Anne P
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.
Center for Innovative Design & Analysis, Department of Biostatistics & Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Int J Hyg Environ Health. 2025 Jan;263:114464. doi: 10.1016/j.ijheh.2024.114464. Epub 2024 Sep 26.
BACKGROUND/OBJECTIVES: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts.
Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood.
We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84).
Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.
背景/目的：孕期暴露于环境空气污染与儿童期不良心脏代谢结局相关。我们之前观察到，孕期黑碳（BC）与幼儿期脂联素呈负相关，脂联素是一种由脂肪细胞分泌的激素。DNA甲基化的改变被认为是将子宫内暴露与持久健康影响联系起来的潜在中介因素。
在参与科罗拉多州健康启动研究的532对母婴中，我们进行了一项全基因组关联研究，以探讨孕期暴露于空气污染成分BC与脐带血DNA甲基化之间的关系。使用时空预测模型估计母亲居住地的孕期平均环境BC。使用Illumina 450K芯片测量DNA甲基化。我们使用多元线性回归来估计孕期环境BC与429,246个半胱氨酸-磷酸-鸟嘌呤位点（CpG）之间的关联，并对潜在混杂因素进行调整。我们使用DMRff和ENmix-combp识别差异甲基化区域（DMR）。在一部分参与者（n = 243）中，我们研究了DNA甲基化作为孕期环境BC与儿童期较低脂联素之间关联的潜在中介因素。
在进行多重检验校正后，我们确定了44个与孕期平均环境BC相关的CpG。注释到顶级CpG的几个基因在免疫系统中具有已报道的功能。DMRff和ENmix-combp共同识别出24个DMR。发现位于2号染色体上并注释到UNC80基因的一个CpG（cg01123250）介导了孕期BC对儿童期脂联素影响的约20%，尽管置信区间较宽（95%CI：3，84）。
孕期BC与基因组中多个位点和区域的脐带血DNA甲基化相关。DNA甲基化可能部分介导孕期BC与儿童期心脏代谢结局之间的关联。
