Abstract
BackgroundAsthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers.ResultsWe examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma.ConclusionsWe identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0163-4) contains supplementary material, which is available to authorized users.
Highlights
Asthma is the most common chronic inflammatory disorder in children
Our analyses focused on identifying differentially methylated positions (DMPs) associated with asthma in (i) all asthma-discordant MZ twins at age 10 (Additional file 1: Figure S1A) and (ii) a sub-group with persistent asthma who were discordant for asthma at age 10 and at age 18 (Additional file 1: Figure S1B)
The top-ranked DMP associated with persisting asthma is located 8 kb downstream of the transcriptional start site (TSS) of the HLX gene, which has been previously implicated in childhood asthma [29, 30]
Summary
Asthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. Complex and highly heterogeneous disorder characterized by recurring episodes of breathlessness and wheezing [1]. Asthma affects approximately 235 million people worldwide and is the most prevalent chronic inflammatory disorder in children [2]. Asthma is known to involve complex interplay between genetic and environmental risk factors. Genome-wide association studies (GWAS) have identified a small number of common risk variants robustly associated with asthma, including a gene-rich locus on chromosome
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