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

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-01-12 DOI:10.1038/s41467-025-55909-8

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 De Weerth, Nicole R. Bush, Kieran J. O’Donnell, S. Evelyn Stewart, Michael S. Kobor

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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.

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口腔上皮细胞年龄相关变化对儿童表观遗传生物标志物研究的影响

颊拭子是主要由颊上皮细胞组成的异质性样本，广泛用于儿科DNA甲基化研究和生物标志物的创建。然而，在成人中，随着年龄的增长，口腔比例的下降在儿童中仍未得到研究。我们分析了4626名2个月到20岁的正常发育儿童的脸颊拭子。估计的口腔比例在整个儿童期随着实际年龄和预测的表观遗传年龄的增加而下降。然而，在整个青春期，颊部比例与年龄无关。在整个发育范围内，口腔比例的变异性随着年龄的增长而增加。这些趋势与中性粒细胞比例相反。在初始估计中，对口腔比例的校正将与PedBE年龄加速的弱关联减弱到不显著。值得注意的是，颊比例校正减弱了PedBE年龄加速与强迫症的关联，并加强了与日皮质醇斜率的关联。因此，儿童口腔细胞的年龄相关变化是细胞类型敏感研究的关键考虑因素。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.