Understanding Biological Differences in Health and Development

Once we are aware of biological signals present in conjunction with social experiences, it is was necessary that we further investigate what these may indicate for health and development. To date most of the available tools in epigenetics are not appropriate for pediatric populations, so the interpretability of data in the field is especially hindered when examining young children, who also have the most plastic epigenomes. For example, across the lifespan, environmental and stochastic changes accumulate in DNA methylation patterns throughout the genome such that the DNA methylation landscape shows robust associations with age. Epigenetic ‘clocks’ encompass sets of specific sites that are highly accurate predictors of chronological age, proving to be the most robust biomarkers of aging to date. Strikingly, higher epigenetic age than chronological age, or age acceleration, significantly associates with morbidity, mortality, and cumulative stress in aging cohorts. However, these findings have only been verified in adult populations – yet aging and maturation, especially from a biological fitness perspective, are not synonymous.

It is for this reason that Dr. Merrill conceptualized, wrote, budgeted, organized, and is the co-investigator on the Childhood Epigenetic Age Deviations and Developmental Differences (CEAD3) grant that was funded by the Canadian Institutes of Health Research (CIHR). The goal of this project is to use thousands of buccal epithelial samples from children around the world to characterize the confounders, trajectories, and developmental interpretations that can be made from studying pediatric epigenetic age with the pediatric buccal epigenetic (PedBE) clock created by Dr. Michael Kobor. In this project we are specifically addressing three aims: examine how intrinsic factors, such as sex and genetic ancestry, may confound age outcomes; determine the developmental significance and associations with the clock in multiple domains; and investigate the usefulness of changes to pediatric epigenetic age as an outcome of social and nutritional interventions. To this end, our in-preparation work showcases the consistent association of cell type proportion differences with age in young children, and how to address this in studies employing the PedBE clock across ages, populations, and sexes in over 2,000 pediatric samples. In addition to this work, Dr. Merrill is leading the creation of a pediatric blood epigenetic clock, as DNA methylation is tissue specific, and many pediatric samples are from venous blood or dried blood spots. This clock will be characterized like the PedBE clock and created from more than 4,000 pediatric samples using two machine learning.

Dr. Merrill is also leading investigations on how health and development is reflected in children’s DNA methylation. Specifically, DNA methylation predictions of upper respiratory infections in young children and associations of DNA methylation and later developmental perturbations with prenatal endocrine disrupting chemical exposure, such as phthalates and microplastics. We also combined these questions by looking at the potential sex specific mediation of DNA methylation in the association of prenatal phthalate exposure and childhood upper respiratory infections – which we found to be substantial for boys, but not girls in our study. By exploring environmental and health consequences also related to development and molecular differences, as well as the creation and characterization of tools to interpret these findings, we can build foundations to better understand and utilize findings in social epigenetics.

Research aim:
Biological Embedding

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Research Aim:
Psychosocial Interventions

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