A Study in Children Provides Valuable Information for Detecting Associations Between Diseases and Environmental Exposures

The methylome and the metabolome are the profiles with less variability within a same individual, and are therefore the most appropriate for comparing a great number of individuals to find disease biomarkers , according to a study led by ISGlobal, an institution supported by ”la Caixa” Foundation. The study provides valuable information for designing and interpreting studies that seek to associate different ‘omics’ profiles with environmental exposures and diseases.

Since our early days in the uterus, we are exposed to multiple environmental factors that can affect our health. In order to understand how our body responds to different environmental stressors, the so-called ‘omics’ technologies, which allow to detect subtle molecular responses to such factors, are increasingly used. They include for example the analysis of gene modifications (methylome) and their expression (transcriptome), or the type and level of circulating proteins (proteome) or metabolites ( metabolome).

“These types of analyses are of great clinical relevance, since they allow to identify new predictive biomarkers of diseases such as cancer or cardiovascular, neurological or inflammatory diseases very early on, before the apparition of symptoms,” says Léa Maitre, ISGlobal researcher and study coordinator. “However, we first need to better understand if and how these different ‘omic’ profiles vary in healthy people, particularly in children,” she adds.

In this study, the research team looked at 6 different ‘omic’ profiles (DNA methylation, gene expression, micro RNAs, proteins, and metabolites in blood and urine) in156 health children fromfive European countries, in order to analyse the variability between individuals (inter-individual) and within the same person (intra-individual) at two different timepoints (spaced by 6 months). The study was conducted in the framework of the European HELIX project, focused on the early-life exposome.

The results reveal a large range of variability among the different ‘omic’ profiles but, overall, the variation within the same person over time (intra-individual) was higher than that observed between individuals at a given time-point (inter-individual). The most stable profiles were DNA methylation (methylome) and metabolites in blood (metabolome) , while the more variable profile was gene expression (transcriptome). Regarding the methylome, the methylation sites with greater functional relevance were the most stable, and could therefore be used as disease markers in epidemiological studies. DNA methylation can change the activity of a gene and repress its expression. “Our results confirm that differences in methylation patterns can already be detected in early life, even among children with a similar European origin,” says Mariona Bustamente, ISGlobal and CRG researcher, second author of the study.

Regarding the metabolome, the analysis shows that standardising how samples are collected and adjusting for individual factors such as body mass index could help reduce variability and increase the robustness of large-scale studies. The metabolome in serum was shown to be more stable and better reflect the variability between individuals than the urine metabolome.

Therefore, the authors conclude that DNA methylation and metabolites in serum are more informative for studies that perform one single measurement in a large number of individuals , while the less stable profiles such as gene expression can be useful in studies that follow a cohort of individuals over time. The research team also created an ‘omics’ interaction network to obtain a holistic view of the results. This integration of different ‘omic’ layers is the goal of the recent approach called ‘interactome’.

The results of this study will be useful for guiding the design and interpretation of epidemiological studies that seek to associate ‘omic’ profiles with diseases and environmental exposures”, says Léa Maitre.

Reference

Gallego-Paüls, M., Hernández-Ferrer, C., Bustamante, M. et al. Variability of multi-omics profiles in a population-based child cohort. BMC Med 19, 166 (2021). https://doi.org/10.1186/s12916-021-02027-z.