The effect of an individual’s genetic makeup on his/her phenotypic traits (e.g. health status, height, BMI) may be modulated by environmental exposures. For example risk of cardiovascular disease can be partially inherited but also depends on an individual’s life style; e.g., diet, smoking habits, stress. In this project we develop novel experimental and computational approaches to screen, analyze and functionally characterize interactions between genes and environment in 5 different human cell types and 50 cellular treatments (Figure 1).
Across selected cellular environments (cell type/treatment with large changes in gene expression) we then analyze allele specific expression (ASE) to identify genes with GxE interactions. The experimental and computational tools developed by this project have widespread applicability, for example, can be used to tackle the functional basis of human traits in other environmental contexts (e.g. other types of stress and hormonal levels) and genetic backgrounds. Our findings will represent the first comprehensive catalog of genetic variants that interact with exposure across 250 cellular environments in determining human complex traits.