Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, 94720, USA.
Department of Population Medicine, Division of Chronic Disease Research Across the Lifecourse, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
Nat Commun. 2019 Jul 12;10(1):3095. doi: 10.1038/s41467-019-11058-3.
The nasal cellular epigenome may serve as biomarker of airway disease and environmental response. Here we collect nasal swabs from the anterior nares of 547 children (mean-age 12.9 y), and measure DNA methylation (DNAm) with the Infinium MethylationEPIC BeadChip. We perform nasal Epigenome-Wide Association analyses (EWAS) of current asthma, allergen sensitization, allergic rhinitis, fractional exhaled nitric oxide (FeNO) and lung function. We find multiple differentially methylated CpGs (FDR < 0.05) and Regions (DMRs; ≥ 5-CpGs and FDR < 0.05) for asthma (285-CpGs), FeNO (8,372-CpGs; 191-DMRs), total IgE (3-CpGs; 3-DMRs), environment IgE (17-CpGs; 4-DMRs), allergic asthma (1,235-CpGs; 7-DMRs) and bronchodilator response (130-CpGs). Discovered DMRs annotated to genes implicated in allergic asthma, Th2 activation and eosinophilia (EPX, IL4, IL13) and genes previously associated with asthma and IgE in EWAS of blood (ACOT7, SLC25A25). Asthma, IgE and FeNO were associated with nasal epigenetic age acceleration. The nasal epigenome is a sensitive biomarker of asthma, allergy and airway inflammation.
鼻腔细胞表观基因组可能作为气道疾病和环境反应的生物标志物。我们从前鼻采集了 547 名儿童(平均年龄 12.9 岁)的鼻腔拭子,并使用 Infinium MethylationEPIC BeadChip 测量 DNA 甲基化(DNAm)。我们对当前哮喘、过敏原致敏、过敏性鼻炎、呼出气一氧化氮分数(FeNO)和肺功能进行了鼻腔表观基因组全关联分析(EWAS)。我们发现了多个差异甲基化 CpG(FDR<0.05)和区域(DMR;≥5-CpG,FDR<0.05),与哮喘(285-CpG)、FeNO(8,372-CpG;191-DMR)、总 IgE(3-CpG;3-DMR)、环境 IgE(17-CpG;4-DMR)、过敏性哮喘(1,235-CpG;7-DMR)和支气管扩张剂反应(130-CpG)有关。发现的 DMR 注释到了与过敏性哮喘、Th2 激活和嗜酸性粒细胞增多有关的基因(EPX、IL4、IL13),以及以前与血液 EWAS 中哮喘和 IgE 相关的基因(ACOT7、SLC25A25)。哮喘、IgE 和 FeNO 与鼻腔表观遗传年龄加速有关。鼻腔表观基因组是哮喘、过敏和气道炎症的敏感生物标志物。