Abstract
We aim to study DNA methylation (DNAm) variations associated with childhood asthma. 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. 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. We identified novel DNAm variations associated with childhood asthma and suggested new disease-contributing epigenetic mechanisms.
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