Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Merlijn 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 Berge, Martijn C. Nawijn, Yang Li, Wei Chen, Louis J. Bont, Klaus Bønnelykke, Juan C. Celedón, Gerard H. Koppelman and Cheng-Jian Xu ()
Additional contact information
Merlijn Breugel: University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology
Cancan Qi: University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology
Zhongli Xu: UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh
Casper-Emil T. Pedersen: COPSAC (Copenhagen Prospective Study on Asthma in Childhood), Herlev and Gentofte Hospital
Ilya Petoukhov: MIcompany
Judith M. Vonk: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
Ulrike Gehring: Utrecht University
Marijn Berg: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
Marnix Bügel: MIcompany
Orestes A. Carpaij: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
Erick Forno: UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh
Andréanne Morin: University of Chicago
Anders U. Eliasen: COPSAC (Copenhagen Prospective Study on Asthma in Childhood), Herlev and Gentofte Hospital
Yale Jiang: UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh
Maarten Berge: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
Martijn C. Nawijn: University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
Yang Li: Centre for Individualized Infection Medicine (CiiM), a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research
Wei Chen: UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh
Louis J. Bont: University Medical Centre Utrecht
Klaus Bønnelykke: COPSAC (Copenhagen Prospective Study on Asthma in Childhood), Herlev and Gentofte Hospital
Juan C. Celedón: UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh
Gerard H. Koppelman: University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology
Cheng-Jian Xu: Centre for Individualized Infection Medicine (CiiM), a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-35088-6

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