The basic research arm of the lab is concerned with understanding the impact that human lifestyle transitions are having on human physiology. Our motivation is the fact that chronic diseases, including diabetes, heart failure, asthma, and depression, are all increasing in prevalence world-wide, in association with people moving from rural to urban settings. We are thus contrasting gene expression profiles among people living in villages and cities in different places around the world, and studying the genetic basis of the enormous differences that we observe. This “GOGE” (Genetics of Gene Expression) approach unifies whole genome microarray analysis with genome-wide association studies. In future we plan to use other quantitative genomic strategies including metabolomics and next-gen RNASeq.
Our first study site was the Souss region of southern Morocco. Working with the International Foundation for the Conservation and Development of Wildlife in Agadir, graduate student Youssef Idaghdour performed GOGE on Arab and Amazigh populations in Agadir and nearby rural villages, and found that significant regulatory polymorphisms are not affected by environmental variables, which neveretheless impact half the immune transcriptome. In the next few years we will conduct similar studies in Fiji (in collaboration with the Fiji School of Medicine in Suva) and likely several other locations in Central America, Asia and Africa.
In parallel, we are partnering with the Emory Predictive Health Institute in midtown Atlanta on GOGE of a diverse city population. Study participants have been deeply phenotyped for a wide range of traits ranging from bone density through cardiac function to cognition, and return on a regular basis for follow-up. We also have the opportunity to study the effect of dietary manipulation and to experimentally perturb the immune system. Together with the other human transition projects we intend to gain a comprehensive understanding of the joint contributions of nature and nurture for genome function in the blood.