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The human early-life exposome (HELIX): project rationale and design.

Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ - Environ. Health Perspect. (2014)

Bottom Line: Human research on this topic has generally focused on single exposure-health effect relationships.HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood.As proof of concept, it will form an important first step toward the life-course exposome.

View Article: PubMed Central - PubMed

Affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

ABSTRACT

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome.

Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project.

Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures.

Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

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Related in: MedlinePlus

Timeline of the omics analysis.
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f4: Timeline of the omics analysis.

Mentions: Research area 4: integrating molecular exposure signatures. High-throughput molecular biology “omics” techniques (such as metabolomics, proteomics, transcriptomics, epigenomics) have important potential for broad and untargeted characterization of the internal exposome (Ellis et al. 2012; Hebels et al. 2013). Here, the interest is in the identification of exposure biomarkers and mechanistic pathways. Research area 4 will determine molecular signatures associated with environmental exposures through the measurement of endogenous and xenobiotic metabolite profiles in blood and urine, proteins in plasma, and coding and small noncoding RNAs (including miRNAs; microRNAs) and DNA methylation in whole blood. Omics tools will be employed mainly in the subcohort of 1,200 children with newly collected biosamples at 6–9 years of age; the use of new samples ensures comparability between techniques and cohorts (Figure 4, Table 3; see also Supplemental Material, Detailed description of omics techniques to be used in HELIX, pp. 4–6). The use of a similar time point for all omics techniques also allows integration of the different techniques during data analysis. Genotyping is available already in most of the cohorts and will be completed where needed. Two main limitations in epidemiological studies aiming to use omics biomarkers are tissue and intraindividual variability. Omics profiles are tissue specific, and the tissue of interest can usually not be obtained (e.g., adipose tissue, brain tissue). The focus of HELIX is thus on markers in systemic biological samples (blood, urine) to evaluate the use of omics biomarkers as markers of exposure changes in (larger) epidemiological studies. Omics profiles change over time in the same person; a cross-omics paper with three repeat analyses in 16 subjects over 1 month showed that intraindividual variability for metabolomics and transcriptomics was found to be lower than interindividual variability for almost all the biomarkers (Gruden et al. 2012). However, some sets of markers were highly variable within the same subject and thus cannot be used directly in epidemiological studies. Further, longer time periods of 1 month are likely to give higher intraindividual variability. HELIX will make some progress toward characterizing intra- and interindividual variability in the metabolomics and transcriptomics markers by analyzing repeat biological samples collected in the panel studies in different seasons.


The human early-life exposome (HELIX): project rationale and design.

Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ - Environ. Health Perspect. (2014)

Timeline of the omics analysis.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048258&req=5

f4: Timeline of the omics analysis.
Mentions: Research area 4: integrating molecular exposure signatures. High-throughput molecular biology “omics” techniques (such as metabolomics, proteomics, transcriptomics, epigenomics) have important potential for broad and untargeted characterization of the internal exposome (Ellis et al. 2012; Hebels et al. 2013). Here, the interest is in the identification of exposure biomarkers and mechanistic pathways. Research area 4 will determine molecular signatures associated with environmental exposures through the measurement of endogenous and xenobiotic metabolite profiles in blood and urine, proteins in plasma, and coding and small noncoding RNAs (including miRNAs; microRNAs) and DNA methylation in whole blood. Omics tools will be employed mainly in the subcohort of 1,200 children with newly collected biosamples at 6–9 years of age; the use of new samples ensures comparability between techniques and cohorts (Figure 4, Table 3; see also Supplemental Material, Detailed description of omics techniques to be used in HELIX, pp. 4–6). The use of a similar time point for all omics techniques also allows integration of the different techniques during data analysis. Genotyping is available already in most of the cohorts and will be completed where needed. Two main limitations in epidemiological studies aiming to use omics biomarkers are tissue and intraindividual variability. Omics profiles are tissue specific, and the tissue of interest can usually not be obtained (e.g., adipose tissue, brain tissue). The focus of HELIX is thus on markers in systemic biological samples (blood, urine) to evaluate the use of omics biomarkers as markers of exposure changes in (larger) epidemiological studies. Omics profiles change over time in the same person; a cross-omics paper with three repeat analyses in 16 subjects over 1 month showed that intraindividual variability for metabolomics and transcriptomics was found to be lower than interindividual variability for almost all the biomarkers (Gruden et al. 2012). However, some sets of markers were highly variable within the same subject and thus cannot be used directly in epidemiological studies. Further, longer time periods of 1 month are likely to give higher intraindividual variability. HELIX will make some progress toward characterizing intra- and interindividual variability in the metabolomics and transcriptomics markers by analyzing repeat biological samples collected in the panel studies in different seasons.

Bottom Line: Human research on this topic has generally focused on single exposure-health effect relationships.HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood.As proof of concept, it will form an important first step toward the life-course exposome.

View Article: PubMed Central - PubMed

Affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

ABSTRACT

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome.

Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project.

Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures.

Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Show MeSH
Related in: MedlinePlus