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

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, Ai Ling Teh, Michael J. Meaney, Andrea Gonzalez, Jennie G. Noll, Carolina Weerth, Nicole R. Bush, Kieran J. O’Donnell, S. Evelyn Stewart and Michael S. Kobor ()
Additional contact information
Sarah M. Merrill: University of Massachusetts Lowell
Chaini Konwar: University of British Columbia
Fizza Fatima: University of British Columbia
Kristy Dever: University of British Columbia
Julia L. MacIsaac: University of British Columbia
Nicole Letourneau: University of Calgary
Gerald F. Giesbrecht: University of Calgary
Deborah Dewey: University of Calgary
Gillian England-Mason: University of Calgary
Candace R. Lewis: Arizona State University
Dennis Wang: Agency for Science, Technology and Research (A*STAR)
Ai Ling Teh: Agency for Science, Technology and Research (A*STAR)
Michael J. Meaney: Agency for Science, Technology and Research (A*STAR)
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
Michael S. Kobor: University of British Columbia

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-55909-8

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