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Epigenomics. 2018 May;10(5):629-641. doi: 10.2217/epi-2017-0127. Epub 2018 Apr 25.

Nasal DNA methylation is associated with childhood asthma.

Author information

1
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
2
Pyrosequencing Lab for Genomic & Epigenomic Research, Cincinnati, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
3
Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
4
Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA.
5
Center for Autoimmune Genomics & Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
6
Divisions of Biomedical Informatics & Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
7
Division of Biostatistics & Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
8
Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.

Abstract

AIM:

We aim to study DNA methylation (DNAm) variations associated with childhood asthma.

METHODS:

Nasal DNAm was compared between sibling pairs discordant for asthma, 29 sib pairs for genome-wide association studies and 54 sib pairs for verification by pyrosequencing. Associations of methylation with asthma symptoms, allergy and environmental exposures were evaluated. In vitro experiments and functional genomic analyses were performed to explore biologic relevance.

RESULTS:

Three CpGs were associated with asthma. cg14830002 was associated with allergies in nonasthmatics. cg23602092 was associated with asthma symptoms. cg14830002 and cg23602092 were associated with traffic-related air pollution exposure. Nearby genes were transcriptionally regulated by diesel exhaust, house dust mite and 5-aza-2'-deoxycytidine. Active chromatin marks and transcription factor binding were found around these sites.

CONCLUSION:

We identified novel DNAm variations associated with childhood asthma and suggested new disease-contributing epigenetic mechanisms.

KEYWORDS:

DNA methylation; air pollution; childhood asthma; exposures; functional genomics analysis; histone marks; sibling study; transcriptional factor

PMID:
29692198
PMCID:
PMC5992571
[Available on 2019-05-01]
DOI:
10.2217/epi-2017-0127

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