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Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research

Author

Listed:
  • Sarah M. Merrill

    (University of Massachusetts Lowell
    University of British Columbia)

  • Chaini Konwar

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Fizza Fatima

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Kristy Dever

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Julia L. MacIsaac

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Nicole Letourneau

    (University of Calgary
    University of Calgary)

  • Gerald F. Giesbrecht

    (University of Calgary
    University of Calgary
    University of Calgary)

  • Deborah Dewey

    (University of Calgary
    University of Calgary
    University of Calgary)

  • Gillian England-Mason

    (University of Calgary
    University of Calgary)

  • Candace R. Lewis

    (Arizona State University)

  • Dennis Wang

    (Agency for Science, Technology and Research (A*STAR)
    Agency for Science, Technology and Research (A*STAR)
    Imperial College London)

  • Ai Ling Teh

    (Agency for Science, Technology and Research (A*STAR)
    Agency for Science, Technology and Research (A*STAR))

  • Michael J. Meaney

    (Agency for Science, Technology and Research (A*STAR)
    McGill University
    CIFAR)

  • Andrea Gonzalez

    (McMaster University)

  • Jennie G. Noll

    (University of Rochester)

  • Carolina Weerth

    (Donders Institute for Brain, Cognition and Behaviour and Radbound University)

  • Nicole R. Bush

    (University of California)

  • Kieran J. O’Donnell

    (Yale School of Medicine)

  • S. Evelyn Stewart

    (University of British Columbia
    University of British Columbia)

  • Michael S. Kobor

    (University of British Columbia
    University of British Columbia
    University of British Columbia
    CIFAR)

Abstract

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in children’s oral cells is a crucial consideration for cell type-sensitive research.

Suggested Citation

  • Sarah M. Merrill & Chaini Konwar & Fizza Fatima & Kristy Dever & Julia L. MacIsaac & Nicole Letourneau & Gerald F. Giesbrecht & Deborah Dewey & Gillian England-Mason & Candace R. Lewis & Dennis Wang &, 2025. "Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55909-8
    DOI: 10.1038/s41467-025-55909-8
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    References listed on IDEAS

    as
    1. Jennie G. Noll & Ann-Christin Haag & Chad E. Shenk & Michelle F. Wright & Jaclyn E. Barnes & Mojtaba Kohram & Matteo Malgaroli & David J. Foley & Michal Kouril & George A. Bonanno, 2022. "An observational study of Internet behaviours for adolescent females following sexual abuse," Nature Human Behaviour, Nature, vol. 6(1), pages 74-87, January.
    2. Atkinson, Anthony C. & Riani, Marco & Corbellini, Aldo, 2021. "The box-cox transformation: review and extensions," LSE Research Online Documents on Economics 103537, London School of Economics and Political Science, LSE Library.
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