The environment has a direct effect on human phenotypes, including common diseases, and can modify genetic effects on phenotypes through gene-by-environment interactions (GxE). At a cellular level, we can define the environment by the presence of other cell types (e.g. in non-homogeneous tissues), and by the complex of endogenous (e.g. hormonal and metabolic) and exogenous (e.g. pollutants, diet) stimuli that a cell is exposed to. These cellular environments are in turn a complex function of the organismal environment, but are likely to have a more tractable influence on sub-cellular phenotypes such as gene expression. We have applied functional genomics approaches to characterize GxE interactions and their role in complex traits. Within these projects, we developed novel experimental and computational approaches to screen, analyze and functionally characterize genetic variants for complex traits modulated by environmental exposure (Harvey et al, Bioinformatics, 2014, Moyerbrailean et al, Scientific Reports, 2015). In our pioneering studies of allele-specific expression and RNA-processing response to 250 cellular environments, we demonstrated a major role for GxE interactions in complex traits (Moyerbrailean et al, Genome Research, 2016, Richards et al, 2017, resource available at http://genome.grid.wayne.edu/gxebrowser/). We have subsequently applied the molecular GxE framework to study genetic and environmental factors in cardiovascular diseases (CVD) and asthma risk.
.
Luca Lab 