Biomarkers which predict future health outcomes are key to the goals of precision health. Such biomarkers do not have to be involved in the causal pathway of a disease, and their performance is best assessed using statistical tests of clinical performance and evaluation of net health impact. DNA methylation is the most commonly studied epigenetic process and represents a potential biomarker of future health outcomes. We review 25 studies in non-oncological paediatric conditions where DNA methylation biomarkers of future health outcomes are assessed. Whilst a number of positive findings have been described, the body of evidence is severely limited by issues with outcome measures, tissue-specific samples, accounting for sample cell type heterogeneity, lack of appropriate statistical testing, small effect sizes, limited validation, and no assessment of net health impact. Future studies should concentrate on careful study design to overcome these issues, and integration of DNA methylation data with other ‘omic’, clinical, and environmental data to generate the most clinically useful biomarkers of paediatric disease.

中文翻译：

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儿童未来健康结果的 DNA 甲基化生物标志物

预测未来健康结果的生物标志物是精准健康目标的关键。此类生物标志物不必参与疾病的因果途径，最好使用临床表现的统计测试和净健康影响评估来评估其表现。DNA 甲基化是最常研究的表观遗传过程，代表了未来健康结果的潜在生物标志物。我们回顾了 25 项非肿瘤儿科疾病研究，其中评估了未来健康结果的 DNA 甲基化生物标志物。虽然已经描述了一些积极的发现，但由于结果测量、组织特异性样本、对样本细胞类型异质性的解释、缺乏适当的统计测试、效应量小、验证有限、并且没有对净健康影响进行评估。未来的研究应专注于仔细的研究设计以克服这些问题，并将 DNA 甲基化数据与其他“组学”、临床和环境数据相结合，以生成对临床最有用的儿科疾病生物标志物。