The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells
The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells
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DOI：
10.1073/pnas.1820843116
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发表时间：
2020-09-22
影响因子：
11.1
通讯作者：
Kobor, Michael S.
中科院分区：
文献类型：
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作者：
McEwen, Lisa M.;O'Donnell, Kieran J.;Kobor, Michael S.
衰老生物标志物的开发主要集中在成人样本上。表观遗传时钟是一种很有前途的测量生物年龄的工具，在大多数组织和年龄范围内都显示出令人印象深刻的准确性。在成人中，DNA甲基化（DNAm）年龄预测的偏差与几种年龄相关的表型相关，如死亡率和虚弱。然而，在儿童中，这种关联较少，可能是因为与成人相比，儿童人群中的DNAm变化更具动态性。为了解决这一差距，我们的目标是开发一个高度准确的，非侵入性的，生物测量的年龄特定的儿科样本使用颊上皮细胞DNAm。我们从11个不同的年龄在0到20岁之间的典型发育个体群体中收集了1,721个全基因组DNA图谱。使用弹性网络惩罚回归从训练数据集（n = 1，032）中选择94个CpG位点，在单独的测试数据集中评估性能（n = 689）。这94个CpG位点的DNAm高度预测测试组群中的年龄（中值绝对误差= 0.35岁）。儿科-颊-表观遗传（PedBE）时钟在其他队列中进行了表征，展示了纵向数据的准确性，非颊组织和成人年龄范围的性能，以及与产科结局的相关性。用于测量儿童生物学年龄的PedBE工具可能有助于理解在儿童发育过程中塑造DNA甲基化的环境和背景因素，以及它如何反过来与儿童健康和疾病相关。
The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several agerelated phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.