ArticleEnvironment international2020
Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index.
Article in Environment international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 32 citations in OpenAlex.
- Relevance and challenges of exposome studies for environmental health research.Environmental health : a global access science source · 2026Review
- Article
- The predictive utility of the in utero exposome for childhood adiposity in independent and integrated frameworks.Pediatric obesity · 2024Article
- A novel hypothesis-generating approach for detecting phenotypic associations using epigenetic data.Epigenomics · 2024Article
- What if … ? A new hypothesis to approach the relationship between environmental stimuli, biological features, and health.Heliyon · 2023Review
- Multi-omics signatures of the human early life exposome.Nature communications · 2022Article
- Association Studies of Environmental Exposures, DNA Methylation and Children's Cognitive, Behavioral, and Mental Health Problems.Frontiers in genetics · 2022Article
- Advancing tools for human early lifecourse exposome research and translation (ATHLETE): Project overview.Environmental epidemiology (Philadelphia, Pa.) · 2021Review
- Early-life environmental exposure determinants of child behavior in Europe: A longitudinal, population-based study.Environment international · 2021Article
- The Exposome Approach to Decipher the Role of Multiple Environmental and Lifestyle Determinants in Asthma.International journal of environmental research and public health · 2021Review
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Authors and funding
21 authors at 11 institutions in 6 countries.
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Abstract
backgroundThe exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate.
objectivesWe aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI).
methodsAmong 1,173 mother-child pairs from HELIX cohort, 216 exposures ("whole exposome") were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6-10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI ("reduced exposome"). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome.
resultsAmong the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI. DISCUSSION: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI.
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