Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index

Cadiou, Solène; Bustamante, Mariona; Agier, Lydiane; Andrušaitytė, Sandra; Basagaña, Xavier; Carracedo, Ángel; Chatzi, Leda; Gražulevičienė, Regina; González, Juan R.; Gützkow, Kristine B.; Maitre, Léa; Mason, Dan; Millot, Frédéric; Nieuwenhuijsen, Mark; Papadopoulou, Eleni; Santorelli, Gillian; Saulnier, Patrick; Vives, Marta; Wright, John; Vrijheid, Martine; Slama, Rémy

doi:10.1016/j.envint.2020.105622

Cited by 27 publications

(19 citation statements)

References 97 publications

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“…First, Cu is an essential trace element required for numerous cellular processes, including mitochondrial respiration, antioxidant defence, neurotransmitter synthesis, and iron metabolism, among others 64 . In previous HELIX studies, Cu has been related to several health outcomes such as poorer lung function 65 , higher BMI 66,67 and blood pressure 68 , and increased ADHD symptomatology 69 , and here we show potential perturbed pathways that may mediate these associations: immune response, lipid storage and sequestering of metal ions. Second, pathways identified for tobacco smoke (axon development, cognition, cholinergic synapse, insulin signalling, and several types of cancer) were similarly in line with the effects of maternal smoking on health outcomes detected in HELIX children (higher blood pressure 68 and BMI 66 , and increased behavioural problems 69 ).…”

Section: Discussionsupporting

confidence: 64%

Multi-omics signatures of the human early life exposome

et al. 2022

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Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations (https://helixomics.isglobal.org/) will serve to guide future investigation into the biological imprints of the early life exposome.

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Section: Discussionsupporting

confidence: 64%

Multi-omics signatures of the human early life exposome

et al. 2022

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“…Cu is an essential trace element required for numerous cellular processes, including mitochondrial respiration, antioxidant defense, neurotransmitter synthesis, connective tissue formation, pigmentation, peptide amidation and iron metabolism (De Bie et al, 2007). In line with the numerous Cu biological functions, we found in HELIX that child Cu was associated with poorer lung function (Agier et al, 2019), higher BMI (Cadiou et al, 2020; Vrijheid et al, 2020) and higher blood pressure (Warembourg et al, 2019), and increased prevalence of behavioural problems and ADHD symptoms (Maitre et al . under review).…”

Section: Resultsmentioning

confidence: 69%

Multi-omics signatures of the human early life exposome

Maitre

Hernández-Ferrer

Thiel

et al. 2021

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Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1,301 mother-child pairs, we associated individual exposomes consisting of >100 chemical, physical and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, metabolome and proteins) in childhood. We identified 1,170 associations, 249 in pregnancy and 921 in childhood, which revealed potential biological responses and sources of exposure. The methylome best captures the persistent influence of pregnancy exposures, including maternal smoking; while childhood exposures were associated with features from all omics layers, revealing novel signatures for indoor air quality, essential trace elements, endocrine disruptors and weather conditions. This study provides a unique resource (https://helixomics.isglobal.org/) to guide future investigation on the biological effects of the early life exposome.

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“…Two targeted studies focused on blood methylation of the BMI and/or obesity associated CpGs in children. One study reported postnatal levels of PFOS, among a few other exposome factors, to be negatively associated with BMI via differential DNA methylation (Cadiou et al, 2020). In a complementary agnostic approach, the authors identi ed additional postnatal exposures including BPA, PFOS and the number of phthalates, to be generally unexpectedly associated with decreased BMI, an effect mediated by DNA methylation.…”

Section: Dna Methylationmentioning

confidence: 99%

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

Maitre

Jedynak

Gallego³

et al. 2022

Preprint

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Health effects of endocrine disrupting chemicals (EDCs) are challenging to detect in the general population. Omics technologies become increasingly common to identify early biological changes before the apparition of clinical symptoms, to explore toxic mechanisms and to increase biological plausibility of epidemiological associations. This scoping review systematically summarises the application of omics in epidemiological studies assessing EDCs-associated biological effects to identify potential gaps and priorities for future research. Ninety-eight human studies (2004–2021) were identified through database searches (PubMed, Scopus) and citation chaining and focused on phthalates (34 studies), phenols (19) and PFASs (17), while PAHs (12) and recently-used pesticides (3) were less studied. The sample sizes ranged from 10 to 12,476 (median = 159), involving non-pregnant adults (38), pregnant women (11), children/adolescents (15) or both populations studied together (23). Several studies included occupational workers (10) and/or highly exposed groups (11) focusing on PAHs, PFASs and pesticides, while studies on phenols and phthalates were performed in the general population only. Analysed omics layers included metabolic profiles (30, including 14 targeted analyses), miRNA (13), gene expression (11), DNA methylation (8), microbiome (5) and proteins (3). Twenty-one studies implemented targeted multi-assays focusing on clinical routine blood lipid traits, oxidative stress or hormones. Overall, DNA methylation and gene expression associations with EDCs did not overlap across studies, while some EDC-associated metabolite groups, such as carnitines, nucleotides and amino acids in untargeted metabolomic studies, and oxidative stress markers through targeted studies were consistent across studies. Studies had common limitations such as small sample sizes, cross-sectional designs and single sampling for exposure biomonitoring. In conclusion, there is a growing body of evidence evaluating the early biological responses to exposure to EDCs. This review points to a need for larger longitudinal studies, wider coverage of exposures and biomarkers, replication studies and standardisation of research methods and reporting.

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Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index

Cited by 27 publications

References 97 publications

Multi-omics signatures of the human early life exposome

Multi-omics signatures of the human early life exposome

Multi-omics signatures of the human early life exposome

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: a scoping review

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