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Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Author

Listed:
  • Merlijn Breugel

    (University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology
    University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
    MIcompany)

  • Cancan Qi

    (University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology
    University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC))

  • 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)
    University of Groningen, University Medical Center Groningen, Department of Epidemiology)

  • Ulrike Gehring

    (Utrecht University)

  • Marijn Berg

    (University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
    University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology)

  • Marnix Bügel

    (MIcompany)

  • Orestes A. Carpaij

    (University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
    University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology)

  • 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
    Technical University of Denmark)

  • 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)
    University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases)

  • Martijn C. Nawijn

    (University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC)
    University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology)

  • Yang Li

    (Centre for Individualized Infection Medicine (CiiM), a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research
    Centre for Experimental and Clinical Infection Research, a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research
    Radboud University Medical Center)

  • Wei Chen

    (UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh)

  • Louis J. Bont

    (University Medical Centre Utrecht
    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
    University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC))

  • Cheng-Jian Xu

    (Centre for Individualized Infection Medicine (CiiM), a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research
    Centre for Experimental and Clinical Infection Research, a joint venture between Hannover Medical School and Helmholtz Centre for Infection Research
    Radboud University Medical Center
    Hannover Medical School)

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.

Suggested Citation

  • 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 , 2022. "Nasal DNA methylation at three CpG sites predicts childhood allergic disease," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35088-6
    DOI: 10.1038/s41467-022-35088-6
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    References listed on IDEAS

    as
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    Cited by:

    1. Zhaozhong Zhu & Yijun Li & Robert J. Freishtat & Juan C. Celedón & Janice A. Espinola & Brennan Harmon & Andrea Hahn & Carlos A. Camargo & Liming Liang & Kohei Hasegawa, 2023. "Epigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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