Exposomics for childhood asthma

Identification of early interventions to reduce/eliminate asthma - the most common chronic disease among children - could significantly reduce burden on the healthcare system. Large-scale asthma Exposome-Wide Association Studies (ExWAS) could identify potential interventions, however integration of diverse data is required to address association confounders. The CHILD Cohort Study has followed 3,454 healthy Canadian children and their families from early pregnancy, collecting exceptionally diverse data including 24,852 variables from participant questionnaires, clinical data, household and neighbourhood-level exposures, and sample-derived chemical analytic/omic datasets. Here, we report integration of these datasets into the CHILDdb database platform, and use these data to perform ExWAS and machine learning analyses, identifying and further characterizing associations between childhood asthma and 2,954 diverse early exposures (pregnancy to age 5). Significant asthma associations include antibiotic use, human milk components, DEHP phthalate, and mothers prenatal cleaning product/disinfectant exposure. Subsequent analysis revealed epigenetic changes in the cord blood at birth, after prenatal cleaner exposure, and different microbiome and/or inflammatory cytokine changes associated with different asthma-associated exposures in the child. Collective results support asthma as a heterogeneous condition involving multiple etiologies, with associated endotypes, including prenatal exposures with potential transgenerational effects, and suggest targets for early interventions.