One-stop resource for identifying novel biomarkers of environmental exposures in early life

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Researchers now have a unique resource to identify new biomarkers of early life environmental exposures and understand their health effects. This is thanks to a study conducted by the Barcelona Institute for Global Health (ISGlobal), an institution supported by the “la Caixa” Foundation, which systematically documented all the associations between a wide range of early exposures and molecular profiles at different levels, including the epigenome (DNA methylation), transcriptome (gene expression) and metabolome (metabolites). The results, part of the EU-funded ATHLETE project, have been published in Nature Communication and are accessible to the public in https://helixomics.isglobal.org.

Our health greatly depends on the environment in which we live. Indeed, 70 to 90% of the risk of developing a disease is determined by our exposome: a multitude of environmental factors (ie non-genetic factors) to which we are exposed throughout our lives. life. And yet, we still have limited knowledge about what these environmental hazards are, how they interact, and what biological processes they trigger.

Early life is a particularly important time because exposures during these vulnerable developmental periods can have pronounced effects at the molecular level, which may not be clinically detectable until adulthood.”


Martine Vrijheid, Child and Environment Program Manager at ISGlobal

In this study, the research team led by Vrijheid sought to associate multiple chemical, outdoor, social and lifestyle exposures (92 during pregnancy and 116 when children were 6-11 years old), with molecular profiles in the same children (DNA methylation and gene transcription in blood, plasma proteins and metabolites in serum and urine). The analysis included 1,301 mother-infant pairs from the Human Early Life Exposome (HELIX) project, a long-term cohort study in six European countries (Spain, UK, France, Lithuania, Norway and Greece).

“High-performance computing, using massive parallel computers, has allowed us to overcome one of the main challenges faced in big data ‘omics’ analyses,” says co-lead author Juan R Gonzalez. The analysis identified 1,170 significant associations (249 during pregnancy and 921 during childhood) that provide insight into potential biological responses and sources of exposure. Exposures during pregnancy, such as maternal smoking, the heavy metal cadmium, or the trace element molybdenum, were primarily associated with changes in DNA methylation. In contrast, childhood exposures were associated with signatures at all molecular levels, most notably metabolites in serum. The results revealed, for example, that children are exposed to chemical pollutants through their diet.

“We have identified new multi-omic associations with children’s exposure to essential trace elements, weather conditions, indoor air quality, phthalates and parabens”, explains Léa Maitre, first author. “By visualizing these associations as networks, one can better understand whether a given molecular profile is linked to multiple exposures or vice versa, and thus identify potential biological pathways,” she adds.

Indeed, the results provide plausible mechanisms of disease for six groups of exposures: copper, tobacco smoke, childhood indoor air quality, persistent organic pollutants, phthalates and parabens, and weather conditions. For example, children’s exposure to copper was associated with nearly 90 molecular characteristics, including increased levels of C-reactive protein (a marker of inflammation). Temperature, humidity, and other weather conditions in the month prior to sample collection were associated with serum metabolites involved in sleep and depression, proteins involved in thermoregulation, and immune response genes.

“With the rich information on exposomes and molecules available in our catalog, we provide a valuable resource for the scientific community to find biomarkers of exposure, identify sources of exposure, improve understanding of disease mechanisms and, ultimately, promoting public health policies,” concludes Vrijheid. .

Source:

Journal reference:

Master, L. et al. (2022) Multi-omics signatures of the human exposome in early life. Nature Communication. doi.org/10.1038/s41467-022-34422-2.

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