Multi-omics signatures of the human early life exposome.

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.

Identification of autosomal cis expression quantitative trait methylation (cis eQTMs) in children's blood.

Background: The identification of expression quantitative trait methylation (eQTMs), defined as associations between DNA methylation levels and gene expression, might help the biological interpretation of epigenome-wide association studies (EWAS). We aimed to identify autosomal cis eQTMs in children's blood, using data from 832 children of the Human Early Life Exposome (HELIX) project.

Methods: Blood DNA methylation and gene expression were measured with the Illumina 450K and the Affymetrix HTA v2 arrays, respectively.

The early-life exposome and epigenetic age acceleration in children.

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath's Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips.

Performance of approaches relying on multidimensional intermediary data to decipher causal relationships between the exposome and health: A simulation study under various causal structures.

Challenges in the assessment of the health effects of the exposome, defined as encompassing all environmental exposures from the prenatal period onwards, include a possibly high rate of false positive signals. It might be overcome using data dimension reduction techniques. Data from the biological layers lying between the exposome and its possible health consequences, such as the methylome, may help reducing exposome dimension.

Instability of Variable-selection Algorithms Used to Identify True Predictors of an Outcome in Intermediate-dimension Epidemiologic Studies.

Background: Machine-learning algorithms are increasingly used in epidemiology to identify true predictors of a health outcome when many potential predictors are measured. However, these algorithms can provide different outputs when repeatedly applied to the same dataset, which can compromise research reproducibility. We aimed to illustrate that commonly used algorithms are unstable and, using the example of Least Absolute Shrinkage and Selection Operator (LASSO), that stabilization method choice is crucial.

The Exposome Approach to Decipher the Role of Multiple Environmental and Lifestyle Determinants in Asthma.

Asthma is a widespread respiratory disease caused by complex contribution from genetic, environmental and behavioral factors. For several decades, its sensitivity to environmental factors has been investigated in single exposure (or single family of exposures) studies, which might be a narrow approach to tackle the etiology of such a complex multifactorial disease. The emergence of the exposome concept, introduced by C.

Urinary metabolite quantitative trait loci in children and their interaction with dietary factors.

Human metabolism is influenced by genetic and environmental factors. Previous studies have identified over 23 loci associated with more than 26 urine metabolites levels in adults, which are known as urinary metabolite quantitative trait loci (metabQTLs). The aim of the present study is the identification for the first time of urinary metabQTLs in children and their interaction with dietary patterns.

In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children.

Background: The adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows.

Early-Life Environmental Exposures and Childhood Obesity: An Exposome-Wide Approach.

Background: Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups.

Objectives: Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach.

Methods: The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y.

Challenges Raised by Mediation Analysis in a High-Dimension Setting.

Background: Mediation analysis is used in epidemiology to identify pathways through which exposures influence health. The advent of high-throughput (omics) technologies gives opportunities to perform mediation analysis with a high-dimension pool of covariates.

Objective: We aimed to highlight some biostatistical issues of this expanding field of high-dimension mediation.

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

Background: The 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.

Objectives: We 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).