Unique resource for identifying new biomarkers of early life environmental exposures

Unique resource for identifying new biomarkers of early life environmental exposures

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 led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by the “la Caixa” Foundation, which systematically documented all the links between a wide range of early life 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, were published in Nature Communications and are publicly available in https://helixomics.isglobal.org.

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

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

Martine Vrijheid, head of the Childhood and Environment program at ISGlobal

In this study, the research team led by Vrijheid aimed to compare multiple chemical, outdoor, social and lifestyle exposures (92 in 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 from the Human Early Life Exposome (HELIX) project, a long-term cohort study in six European countries (Spain, United Kingdom, France, Lithuania, Norway and Greece).

“High-performance computing using massively parallel computers allowed us to overcome one of the biggest challenges in analyzing large ‘omic’ data,” says Juan R. Gonzalez, senior co-author. The analysis identified 1,170 significant associations (249 in pregnancy and 921 in childhood), providing 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 mostly associated with changes in DNA methylation. In contrast, childhood exposures were associated with signatures at all molecular levels, particularly serum metabolites. For example, the results showed that children are exposed to chemical pollutants through their diet.

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“We identified novel multi-omics associations with children’s exposure to essential trace elements, weather conditions, indoor air quality, and phthalates and parabens,” says Léa Maitre, lead author. “By visualizing these associations as networks, we can better understand whether a given molecular profile is associated with multiple exposures or vice versa, thereby identifying potential biological pathways,” she adds.

In fact, the results provide plausible disease mechanisms for six exposure groups: copper, tobacco smoke, indoor air quality during childhood, persistent organic pollutants, phthalates and parabens, and weather conditions. For example, children's exposure to copper has been linked to nearly 90 molecular traits, including increased levels of C-reactive protein (an inflammatory marker). Temperature, humidity, and other weather conditions in the month before sampling were associated with serum metabolites involved in sleep and depression, proteins involved in thermoregulation, and immune response genes.

“With the rich exposome and molecular information available in our catalog, we provide the scientific community with a valuable resource to find exposure biomarkers, identify sources of exposure, improve understanding of disease mechanisms, and ultimately advance public health policy,” concludes Vrijheid.

Source:

Barcelona Institute for Global Health (ISGlobal)

Reference:

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

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