Nasal DNA methylation profiling of asthma and rhinitis

BACKGROUND: Epigenetic signatures in the nasal epithelium, which is a primary interface with the environment and an accessible proxy for the bronchial epithelium, might provide insights into mechanisms of allergic disease. OBJECTIVE: We aimed to identify and interpret methylation signatures in nasal epithelial brushes associated with rhinitis and asthma. METHODS: Nasal epithelial brushes were obtained from 455 children at the 16 year follow-up of the Dutch PIAMA birth cohort study. Epigenome-wide association studies (EWAS) were performed on asthma, rhinitis and asthma and/or rhinitis (AsRh) using logistic regression, and top results were replicated in two independent cohorts of African American and Puerto Rican children. Significant CpG sites (CpGs) were related to environmental exposures (pets, active and passive smoking and molds) during secondary school, and correlated to gene expression by RNA-sequencing (n=244). RESULTS: The EWAS identified CpGs significantly associated with rhinitis (n=81) and AsRh (n=75), but not with asthma. We significantly replicated 62 /81 CpGs with rhinitis, and 60/75 with AsRh, as well as one CpG with asthma. Methylation of cg03565274 was negatively associated with AsRh, and positively associated with pets exposure during secondary school. DNA methylation signals associated with AsRh were mainly driven by specific IgE positive subjects. DNA methylation related to gene transcripts that were enriched for immune pathways, and expressed in immune and epithelial cells. Nasal CpGs performed well in predicting AsRh. CONCLUSIONS: We identified replicable DNA methylation profiles of asthma and rhinitis in nasal brushes. Pets exposure may affect nasal epithelial methylation in relation to asthma and rhinitis. CLINICAL IMPLICATIONS: Nasal DNA methylation profiles may serve as biomarker of asthma and rhinitis, and can be used across different populations to predict the presence of asthma and/or rhinitis in children.