Newswise — Researchers now have a one-stop resource for identifying new biomarkers of environmental exposures early in life 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, which are part of the EU-funded program ATHLETE project, were 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. In fact, 70-90% risk of developing disease is determined by our exposome: a multitude of environmental factors (ie non-genetic factors) to which we are exposed throughout our lives. 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 developmental phases vulnerable periods can have pronounced effects at the molecular level, which may not be clinically detectable until adulthood,” explains Martine VrijheidHead of Childhood and Environment Program at ISGlobal.
In this study, the research team led by Vrijheid aimed to associate several chemical, exterior, social and lifestyle exhibitions (92 during pregnancy and 116 when the 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-child pairs of the Human Early Childhood Exposome (HELIX), 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 in big data ‘omics’ analysis,” says Juan R. González, co-lead author. The analysis identified 1,170 significant associations (249 during pregnancy and 921 during childhood) which provide insight into potential biological reactions and sources of exposure. Exposures during pregnancysuch as maternal smoking, cadmium, a heavy metal, or molybdenum, a trace element, were mainly associated with changes in DNA methylation. In contrast, childhood exhibits were associated with signatures at all molecular levels, more particularly with metabolites in serum. The results revealed, for example, that children are exposed to chemical pollutants through their diet.
“We identified novel multi-omic associations with children’s exposure to essential trace minerals, weather conditions, indoor air quality, phthalates and parabens,” says Lea Master, 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 findings give plausible mechanisms of disease for six groups of exposures: copper, tobacco smoke, indoor air quality during childhood, persistent organic pollutants, phthalates and parabens and meteorological conditions. For instance, copper exposure of children was associated with nearly 90 molecular characteristics, including increased levels of C-reactive protein (a marker of inflammation). Temperature, humidity and other weather conditions during 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 to the scientific community to find the exhibition biomarkersexposure identification sourcesimprove understanding of the disease mechanismsand ultimately the promotion of public health Strategiesconcludes Vrijheid.
Maitre L, Bustamante M, Hernandez-Ferrer C…, González JR, Keun HC, Vrijheid M. Multi-omic signatures of the human exposome in early life. 2022. Nature Comms. https://doi.org/10.1038/s41467-022-34422-2