Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Infancy and early childhood are highly sensitive periods in human development. Experiences during these stages can have deep biological consequences, which in turn impact future health. DNA methylation (DNAme), which refers to a chemical label that can be attached to approximately 30 million sites in the DNA, can regulate the activity of genes, and has been proposed as one of the mechanisms by which early life experiences get biologically embedded. Understanding DNAme variability is valuable because some DNAme patterns are linked to health and disease. Moreover, modifications of this chemical label can be stable across the human lifespan, linking early life experiences to adult health outcomes. In addition to environmental exposures, genetic predisposition can also modify the attachment of this chemical tag. However, how many sites are sensitive to genetic predisposition, environmental exposures, or both, is still not well understood. To address this knowledge gap, I will analyze data from a canadian nation-wide longitudinal cohort (CHILD) that comprise extensive information about children's genetics, as well as physical, chemical, nutritional, and psychosocial exposures. I am developing a statistical methodology to first identify sites in the human genome with variable DNAme levels in children. Then, I will find and characterize the factors that best explain the differences for each of these regions. This study will generate a novel reproducible approach to integrate DNAme, genetic, and exposure data. The findings of this study will contribute to the understanding of how, and under which conditions, individual genetic susceptibility and environmental variables work together to influence the molecular processes that enable early-life experiences to get under our skin. Further, our results may inform personalized medicine approaches on the potential early factors influencing DNAme in disease-associated sites.