The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005 to 2007 to assess polychlorinated biphenyl (PCB) exposures in Anniston, Alabama residents. In 2014, a follow-up study (ACHS-II) was conducted to measure the same PCBs as in ACHS-I and additional compounds e.g., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like non-ortho (cPCBs) substituted PCBs. In this epigenome-wide association study (EWAS), we examined the associations between PCDD, PCDF, and PCB exposures and DNA methylation. Whole blood DNA methylation was measured using Illumina EPIC arrays (n=292). We modeled lipid-adjusted toxic equivalencies (TEQs) for: ΣDioxins (sum of 28 PCDDs, PCDFs, cPCBs, and mPCBs), PCDDs, PCDFs, cPCBs, and mPCBs using robust multivariable linear regression adjusting for age, race, sex, smoking, bisulfite conversion batch, and estimated percentages of six blood cell types. Among all exposures we identified 10 genome-wide (Bonferroni p≤6.74E−08) and 116 FDR (p≤5.00E−02) significant associations representing 10 and 113 unique CpGs, respectively. Of the 10 genome-wide associations, seven (70%) occurred in the PCDDs and four (40%) of these associations had an absolute differential methylation ≥1.00%, based on the methylation difference between the highest and lowest exposure quartiles. Most of the associations (six, 60%) represented hypomethylation changes. Of the 10 unique CpGs, eight (80%) were in genes shown to be associated with dioxins and/or PCBs based on data from the 2019 Comparative Toxicogenomics Database. In this study, we have identified a set of CpGs in blood DNA that may be particularly susceptible to dioxin, furan, and dioxin-like PCB exposures.

安尼斯顿社区健康调查 (ACHS-I) 最初​​于 2005 年至 2007 年进行，以评估阿拉巴马州安尼斯顿居民的多氯联苯 (PCB) 暴露情况。2014 年，进行了一项后续研究 (ACHS-II)，以测量与 ACHS-I 中相同的 PCB 和其他化合物，例如多氯二苯并二恶英 (PCDD)、多氯二苯并呋喃 (PCDF) 和类二恶英非邻位（cPCBs）取代的多氯联苯。在这项表观基因组关联研究 (EWAS) 中，我们检查了 PCDD、PCDF 和 PCB 暴露与 DNA 甲基化之间的关联。使用 Illumina EPIC 阵列测量全血 DNA 甲基化（n=292)。我们使用稳健的多变量线性回归调整年龄、种族、性别、吸烟、亚硫酸氢盐转化批次，以及六种血细胞类型的估计百分比。在所有暴露中，我们确定了 10 个全基因组 (Bonferroni p ≤6.74E-08) 和 116 个 FDR ( p≤5.00E-02) 分别代表 10 和 113 个独特 CpG 的显着关联。根据最高和最低暴露四分位数之间的甲基化差异，在 10 个全基因组关联中，7 个（70%）发生在 PCDD 中，其中 4 个（40%）的甲基化绝对差异≥1.00%。大多数关联（6 个，60%）代表低甲基化变化。根据 2019 年比较毒物基因组学数据库的数据，在 10 个独特的 CpG 中，有 8 个（80%）位于与二恶英和/或 PCB 相关的基因中。在这项研究中，我们确定了血液 DNA 中的一组 CpG，它们可能对二恶英、呋喃和类二恶英 PCB 暴露特别敏感。