Open-source atlas aims to improve use of epigenetic tools in paediatric studies
Researchers at the Erasmus University Rotterdam and University of Bristol worked together to complete the first systematic review of DNA methylation profile scores (MPSs) used in children and young people. The review highlights opportunities for earlier disease research and prevention, while warning that many existing tools may not yet be well suited to paediatric use. It also introduces DEMETRA, a new open-source resource, to help researchers select the most appropriate methylation scores for early-life studies.
Published in eBioMedicine, the review identified 828 unique methylation profile scores across 119 studies, covering a wide range of applications including:
- Environmental exposures
- Biological markers
- Rare genetic syndromes
- Cancer
- Physical and neuropsychiatric health outcomes
DNA methylation is a natural process during which methyl groups are added to our DNA. This helps cells understand which genetic instructions they should be following. Some genes are switched ‘on’ or ‘off’ while our genetic code stays the same.
Methylation profile scores capture patterns of added methyl groups across the human genome (complete set of genetic information) linked to exposures, biological states and disease-related processes. In early-life research, these tools may be valuable because they offer a way to study how environmental and biological influences become embedded during childhood, often before disease develops.
Because DNA methylation changes quickly across infancy, childhood and adolescence, the researchers conclude that early life should be treated as a distinct biological and methodological context rather than simply an extension of adulthood.
The authors say their findings underline the need for more developmentally tuned methylation tools, better reporting standards and more diverse datasets. At present, 65% of the early-life methylation profile scores identified in the review were trained and applied in White or European ancestry samples, raising concerns that a lack of diversity could worsen existing health inequalities if not addressed.
To support more rigorous and transparent research, the team developed DEMETRA (Developmental Methylation Risk Atlas) a searchable online database cataloguing methylation profile scores trained or applied in early life.
DEMETRA includes information on the phenotype being measured, the life stage and tissue in which a score was developed and applied, methodological details, and links to the original studies. The authors say this will help researchers identify suitable tools more quickly and reveal where important gaps remain.
Matthew Suderman, Associate Professor of Epigenetic Epidemiology at the University of Bristol’s MRC Integrative Epidemiology Unit and NIHR Bristol Biomedical Research Centre, said:
“Early life offers a crucial window for understanding how health throughout life is influenced by the world around us.
“Our review shows there is real potential for methylation profile scores to strengthen child health research, but it also makes clear that we cannot assume tools developed in adults will work in the same way in children.
“DEMETRA is an important step towards making this area of research more rigorous, transparent and equitable.”
Looking ahead, the researchers argue that expanding longitudinal early-life DNA methylation datasets, improving methodological consistency, and increasing ancestral diversity will be essential if the field is to achieve the aim of disease prevention through:
- Improved risk stratification
- Risk-reducing interventions
- Early disease detection
