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Epigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study

Author

Listed:
  • Zhaozhong Zhu

    (Harvard Medical School)

  • Yijun Li

    (Harvard T.H.Chan School of Public Health)

  • Robert J. Freishtat

    (Children’s National Hospital
    Children’s National Hospital
    George Washington University School of Medicine and Health Sciences)

  • Juan C. Celedón

    (University of Pittsburgh)

  • Janice A. Espinola

    (Harvard Medical School)

  • Brennan Harmon

    (Children’s National Hospital)

  • Andrea Hahn

    (Children’s National Hospital
    George Washington University School of Medicine and Health Sciences
    Children’s National Hospital)

  • Carlos A. Camargo

    (Harvard Medical School)

  • Liming Liang

    (Harvard T.H.Chan School of Public Health
    Harvard T.H.Chan School of Public Health)

  • Kohei Hasegawa

    (Harvard Medical School)

Abstract

Bronchiolitis is the most common lower respiratory infection in infants, yet its pathobiology remains unclear. Here we present blood DNA methylation data from 625 infants hospitalized with bronchiolitis in a 17-center prospective study, and associate them with disease severity. We investigate differentially methylated CpGs (DMCs) for disease severity. We characterize the DMCs based on their association with cell and tissues types, biological pathways, and gene expression. Lastly, we also examine the relationships of severity-related DMCs with respiratory and immune traits in independent cohorts. We identify 33 DMCs associated with severity. These DMCs are differentially methylated in blood immune cells. These DMCs are also significantly enriched in multiple tissues (e.g., lung) and cells (e.g., small airway epithelial cells), and biological pathways (e.g., interleukin-1-mediated signaling). Additionally, these DMCs are associated with respiratory and immune traits (e.g., asthma, lung function, IgE levels). Our study suggests the role of DNA methylation in bronchiolitis severity.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41300-y
    DOI: 10.1038/s41467-023-41300-y
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    References listed on IDEAS

    as
    1. Michimasa Fujiogi & Yoshihiko Raita & Marcos Pérez-Losada & Robert J. Freishtat & Juan C. Celedón & Jonathan M. Mansbach & Pedro A. Piedra & Zhaozhong Zhu & Carlos A. Camargo & Kohei Hasegawa, 2022. "Integrated relationship of nasopharyngeal airway host response and microbiome associates with bronchiolitis severity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. 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.
    3. Yoshihiko Raita & Marcos Pérez-Losada & Robert J. Freishtat & Brennan Harmon & Jonathan M. Mansbach & Pedro A. Piedra & Zhaozhong Zhu & Carlos A. Camargo & Kohei Hasegawa, 2021. "Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Giacomo Cavalli & Edith Heard, 2019. "Advances in epigenetics link genetics to the environment and disease," Nature, Nature, vol. 571(7766), pages 489-499, July.
    5. Andres Cardenas & Joanne E. Sordillo & Sheryl L. Rifas-Shiman & Wonil Chung & Liming Liang & Brent A. Coull & Marie-France Hivert & Peggy S. Lai & Erick Forno & Juan C. Celedón & Augusto A. Litonjua &, 2019. "The nasal methylome as a biomarker of asthma and airway inflammation in children," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    6. Guillermo Barturen & Elena Carnero-Montoro & Manuel Martínez-Bueno & Silvia Rojo-Rello & Beatriz Sobrino & Óscar Porras-Perales & Clara Alcántara-Domínguez & David Bernardo & Marta E. Alarcón-Riquelme, 2022. "Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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