The nasal methylome as a biomarker of asthma and airway inflammation in children

被引：130

作者：

Cardenas, Andres ^{[1
,2
,3
]}

Sordillo, Joanne E. ^{[2
,3
]}

Rifas-Shiman, Sheryl L. ^{[2
,3
]}

Chung, Wonil ^{[4
]}

Liang, Liming ^{[4
]}

Coull, Brent A. ^{[4
]}

Hivert, Marie-France ^{[2
,3
,5
]}

Lai, Peggy S. ^{[6
]}

Forno, Erick ^{[7
]}

Celedon, Juan C. ^{[7
]}

Litonjua, Augusto A. ^{[8
]}

Brennan, Kasey J. ^{[9
]}

DeMeo, Dawn L. ^{[10
]}

Baccarelli, Andrea A. ^{[9
]}

Oken, Emily ^{[2
,3
]}

Gold, Diane R. ^{[10
,11
]}

机构：

[1] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA

[2] Harvard Med Sch, Dept Populat Med, Div Chron Dis Res Lifecourse, Boston, MA 02215 USA

[3] Harvard Pilgr Hlth Care Inst, Boston, MA 02215 USA

[4] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[5] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[6] Massachusetts Gen Hosp, Pulm Crit Care, Boston, MA 02114 USA

[7] Univ Pittsburgh, Div Pediat Pulm Med, Sch Med, Pittsburgh, PA 15224 USA

[8] Univ Rochester, Div Pediat Pulm Med, Med Ctr, Rochester, NY 14642 USA

[9] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[11] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

EXHALED NITRIC-OXIDE; EPIGENOME-WIDE ASSOCIATION; CELL-TYPE HETEROGENEITY; SERUM IMMUNOGLOBULIN-E; DNA METHYLATION; CHILDHOOD ASTHMA; EPITHELIAL-CELLS; RISK; LUNG; EOSINOPHILS;

D O I：

10.1038/s41467-019-11058-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Bead-Chip. 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.

引用

页数：10

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