Nasal DNA methylation at three CpG sites predicts childhood allergic disease

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  • 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
  • Juan C. Celedón
  • Gerard H. Koppelman
  • Cheng Jian Xu

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.

OriginalsprogEngelsk
Artikelnummer7415
TidsskriftNature Communications
Vol/bind13
ISSN2041-1723
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; Lung Foundation of the Netherlands (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; The Netherlands Ministry of Health, Welfare, and Sport; and the Ubbo Emmius Foundation. Yang Li was supported by an ERC Starting Grant (948207) and the Radboud University Medical Centre Hypatia Grant (2018) for Scientific Research. Cancan Qi was supported by a grant from the China Scholarship Council. Cheng-Jian Xu was supported by the Helmholtz Initiative and Networking Fund (1800167).

Publisher Copyright:
© 2022, The Author(s).

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