Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Merlijn van Breugel, Cancan Qi, Zhongli Xu, Casper Emil T. Pedersen, Ilya Petoukhov, Judith M. Vonk, Ulrike Gehring, Marijn Berg, Marnix Bügel, Orestes A. Carpaij, Erick Forno, Andréanne Morin, Anders U. Eliasen, Yale Jiang, Maarten van den Berge, Martijn C. Nawijn, Yang Li, Wei Chen, Louis J. Bont, Klaus BønnelykkeJuan C. Celedón, Gerard H. Koppelman, Cheng Jian Xu*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)
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Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.

Original languageEnglish
Article number7415
Number of pages13
JournalNature Communications
Issue number1
Publication statusPublished - 1-Dec-2022


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