DNA methylation biomarkers of future health outcomes in children

Abstract

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.

Keywords: Biomarker; DNA methylation; Epigenetics; Pediatrics; Precision medicine.

Fig. 1

Summary of epigenetic mechanisms. There are multiple epigenetic processes that interact to determine whether DNA (Ia) open and accessible to transcription or (IIb) closed and inaccessible to transcription. Epigenetic processes include (II) DNA methylation, which is the methylation of cytosine residues in CpG dinucleotides, (IIIa) histone tail modifications which can facilitate accessible DNA (histone acetylation and methylation) or (IIIb) histone tail modifications which are associated with inaccessible DNA (histone deacetylation and demethylation), (IV) non-coding RNA which interact with DNA and/or other epigenetic processes, and (V) higher-order chromatin structure (image modified from [9])