儿童住宅 PM 暴露与鼻腔甲基组
Residential PM exposure and the nasal methylome in children.
机构信息
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, 2121 Berkeley Way, Berkeley, CA, USA.
出版信息
Environ Int. 2021 Aug;153:106505. doi: 10.1016/j.envint.2021.106505. Epub 2021 Apr 16.
RATIONALE
PMinduced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.
OBJECTIVES
We aimed to study associations of fine particulate matter PM exposure with DNA methylation in nasal cells.
METHODS
We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).
RESULTS
In adjusted analyses, we found 362 CpGs associated with 1-year PM (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM.
CONCLUSION
We observed wide-spread DNAm variability associated with average past year PM exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.
背景
PM 对呼吸健康的不良影响可能是由气道细胞中的表观遗传修饰驱动的。暴露持续时间对气道中表观遗传改变的潜在影响尚不清楚。
目的
我们旨在研究细颗粒物（PM）暴露与鼻腔细胞中 DNA 甲基化的关联。
方法
我们在 Viva 项目中的 503 名儿童（平均年龄 12.9 岁）中进行了鼻腔表观基因组关联分析，并检查了鼻腔采样前的各种暴露持续时间（1 天、1 周、1 个月、3 个月和 1 年）。我们使用居住地址以 1km 分辨率估算平均每日 PM。我们从前鼻孔采集鼻腔拭子，并使用 Illumina MethylationEPIC BeadChip 测量 DNA 甲基化（DNAm）。我们使用 CpG-by-CpG 和区域 DNAm 分析测试了 719,075 个高质量常染色体 CpG，控制了多次比较，并调整了母亲教育、家庭吸烟者、儿童性别、种族/民族、BMI z 分数、年龄、样本采集季节和细胞类型异质性。我们进一步纠正了偏差和基因组膨胀。我们在荷兰的一个队列（PIAMA）中进行了复制检验。
结果
在调整后的分析中，我们发现 362 个 CpG 与 1 年 PM 相关（FDR<0.05），20 个 CpG 通过 Bonferroni 校正（P<7.0x10），10 个差异甲基化区域（DMRs）。在 445 名 PIAMA 参与者（平均年龄 16.3 岁）中，203 个可用 CpG 中有 11 个在 P<0.05 时复制。我们观察到与细胞周期、免疫和炎症反应相关的基因附近/处的 DNAm 差异。在样本采集前 1 天、1 周或 1 个月，没有 CpG 或区域与 PM 水平相关，但有 2 个 CpG 与过去 3 个月的 PM 相关。
结论
我们观察到与过去一年平均 PM 暴露相关的广泛的 DNAm 可变性，但未检测到与短期暴露相关的可变性。我们的结果表明，鼻腔 DNAm 标记反映了慢性空气污染暴露。
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