Nasal DNA methylation profiling of asthma and rhinitis

Cancan Qi, Yale Jiang, Ivana V Yang, Erick Forno, Ting Wang, Judith M Vonk, Ulrike Gehring, Henriëtte A Smit, Edith B Milanzi, Orestes A Carpaij, Marijn Berg, Laura Hesse, Sharon Brouwer, Jonathan Cardwell, Cornelis J Vermeulen, Edna Acosta-Pérez, Glorisa Canino, Nadia Boutaoui, Maarten van den Berge, Sarah A TeichmannMartijn C Nawijn, Wei Chen, Juan C Celedón, Cheng-Jian Xu, Gerard H Koppelman

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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 Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Epigenome-wide association studies were performed on children with asthma, rhinitis, and asthma and/or rhinitis (AsRh) by using logistic regression, and the top results were replicated in 2 independent cohorts of African American and Puerto Rican children. Significant CpG sites were related to environmental exposures (pets, active and passive smoking, and molds) during secondary school and were correlated with gene expression by RNA-sequencing (n = 244). Results: The epigenome-wide association studies identified CpG sites significantly associated with rhinitis (n = 81) and AsRh (n = 75), but not with asthma. We significantly replicated 62 of 81 CpG sites with rhinitis and 60 of 75 with AsRh, as well as 1 CpG site with asthma. Methylation of cg03565274 was negatively associated with AsRh and positively associated with exposure to pets 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 CpG sites performed well in predicting AsRh. Conclusions: We identified replicable DNA methylation profiles of asthma and rhinitis in nasal brushes. Exposure to pets may affect nasal epithelial methylation in relation to asthma and rhinitis.

Original languageEnglish
Pages (from-to)1655-1663
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Issue number6
Early online date14-Jan-2020
Publication statusPublished - Jun-2020


  • Asthma
  • rhinitis
  • united airways
  • epigenetics
  • environmental exposure
  • RISK
  • IGE

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