The Molecular Mechanisms of the Human Early Life Exposome (HELIX) Project

Abstract

The exposome is defined as all the exposures from conception to death. Prenatal and early life exposome are thought to be more harmful to health than postnatal exposures. The aims of the Human Early Life Exposome (HELIX) project are to characterize the early life exposome with the aim to associate it with child health outcomes and relate it to omics molecular mechanisms. 1,300 children of 6-10 years from 6 different European cohorts (BiB - Born in Bradford, United Kingdom; EDEN - Étude des Déterminants pré et postnatals du développement et de la santé de l’ENfant, France; INMA - Infancia y Medio Ambiente, Spain; KANC - Kaunus Cohort, Lithuania; MoBa - Norwegian Mother and Child Cohort Study, Norway and Rhea - Greece) were followed using the same protocol. More than 200 exposures including the outdoor exposome (air pollution, build environment, noise), the individual exposome (cotinine, metals, POPs, PFAS, phthalates, phenols and organophosphates) was measured. In the HELIX project 3 main health outcomes were assessed: i) growth and cardio-metabolic phenotype, ii) lung function, asthma and allergy, iii) neurodevelopment and behaviour. Molecular signatures at the age of 6-10y were obtained: blood DNA methylation, gene and miRNA transcription, plasma proteins and serum and urinary metabolites. Specifically, information about children’s cognitive development is obtained using six different tests (N-back task, Attention Network Test, Finger Tapping test, Raven’s Colored Progressive Matrices, Trail-Making Test, Strengths and Difficulties Questionnaire, Child Behavior Checklist and Conner’s Rating Scale Revised short form). Linear regression models will be used to look for association between cognitive and behavioral outcomes. In parallel, linear regressions models adjusted for main covariates (cohort, sex, age and standardized BMI) will be used to find molecular biomarkers associated with each exposure, bot prenatal and postnatal. To provide with a measure of the variability of the omics profiles (metabolome, preoteome, miRNA and gene transcriptome and methylome) be explained by both prenatal and postnatal exposome, the global effect of the exposome on the omics profiles will be analyzed using the O2PLS (orthogonal two partial least squares) regression.

Date
Event
NIEHS Environmental Contributors to Autism: Comprehensive Grantee Meetinge
Location
BarcelonaBiomedical Research Parck, Barcelona, Spain