Integrated Personalized Epigenome Profiling and the Effect of Dietary Exposure on Individuals at Risk for Type-2-Diabetes

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 DESCRIPTION (provided by applicant): Disease risk is governed by complex interactions between an individual's genetic background and environmental exposures, yet very little is currently understood about how environmental factors influence the genome. Recent studies suggest that dietary exposure, a key environmental factor with roles in the pathogenesis of obesity, type-2-diabetes (T2D), and other complex diseases, modulates gene expression through epigenetic mechanisms. It is therefore likely that the epigenome, defined here as the overall epigenetic profile of an individual in a given cell type, represents a dynamic, reprogrammable interface through which dietary exposure shapes cellular function and disease susceptibility. Here we propose to comprehensively characterize the epigenome in individuals at high- and low-risk for developing T2D during the course of short- term overfeeding. Personalized epigenome profiles will be generated by mapping both chromatin accessibility and DNA methylation patterns in peripheral blood mononuclear cells, and integrated with transcriptomic, proteomic, and metabolomic analyses. This proposal represents the first personalized, integrative epigenome mapping study of its kind. We hypothesize that changes in diet will correlate with measurable, dynamic epigenetic signatures, which will provide important insight into the mechanisms underlying gene-environment interactions and yield clinically-relevant biomarkers for both exposure and disease.