Dr. Jason Stein (Associate Professor, Genetics and Neuroscience Center) was awarded a new U01 grant from the National Institute of Aging (NIA) for his project titled “AD GxE: in vivo and in vitro modeling of gene x environment interactions”.
Common genetic variants identified through genome-wide association studies have been reproducibly associated with risk for Alzheimer’s disease (AD), but the function of many risk variants are unknown and likely context-specific. At the same time, several environmental exposures have been implicated in AD and dementia, including particulate matter air pollution (PM2.5), heavy metals (especially lead (Pb)), and infections. The hypothesis guiding the study is that the genetic architecture of AD includes gene-environment interactions (GxE) between common, non-coding variants and environmental exposure. The grant proposes to identify these GxE using an in vitro model, “GxE in a dish”, using the inherent genetic diversity in a population of neural cells exposed to AD-relevant environmental exposures.