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 nononcological 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.

Regulation of Il6 expression by single CpG methylation in downstream of Il6 transcription initiation site

“…It is still unclear whether this change in DNA methylation is beneficial. However, some recent reports have proposed that several CpG dinucleotides can be used as biomarkers to predict treatment outcomes and illness severity for many diseases, including cancer, pediatric diseases, autoimmune diseases, and even the recent COVID-19 ( Nile et al., 2008 ; Claus et al., 2012 ; Shanthikumar et al., 2020 ; de Moura et al., 2021 ). Furthermore, a single CpG dinucleotide has a greater advantage in targeted therapy for suppressing gene expression in cells, as it has high specificity and creates fewer off-target effects.…”

Epigenetics and Responsibility

“…Global and gene-specific methylation patterns have been associated with different individual behaviours, social conditions, environmental exposures and lifestyles. Although the causal implication of epigenetic modifications in disease aetiology is still debated (Shanthikumar et al, 2020), several researchers have underlined the practical utility of this information (Cooney, 2007;Fiorito et al, 2019). Epigenetic modifications are not only regarded as a footprint of experiences, environmental exposures and life trajectories, but allegedly also offer an insight into the mechanisms of health and disease (Cavalli and Heard, 2019).…”

Environmental and Genetic Traffic in the Journey from Sperm to Offspring

“…DNA methylation, the transfer of a methyl group from S-adenyl methionine (SAM) to the fifth carbon of a cytosine residue, mediated by DNA methyltransferases, modulates gene expression, silences transposons and endogenous retroviral sequences, inactivates the X chromosome, and affects genomic imprinting [193]. In eukaryotes, gene expression may be governed in a variety of ways, but the methylation of DNA is a typical epigenetic signaling mechanism that cells utilize to keep genes in the "off" state.…”