Doctoral Dissertation Research: Investigating the genetic and environmental history of type 2 diabetes

Past and current human populations experienced drastically different environments and ways of life. Consequently, researchers hypothesize that a mismatch between past adaptations and modern environments is contributing to the current rise in non-communicable diseases (e.g., type 2 diabetes, obesity, cardiovascular disease). The concept of evolutionary mismatch suggests that disease-associated genes were beneficial, and thus selected for, in past environments. In modern ones, however, these same genetic variants may lead to negative health consequences. This study examines the evolutionary history of genetic variants associated with type 2 diabetes by: (1) determining if there is evidence of past positive selection, and (2) testing whether genetic variants that were selected in the past interact with current environmental factors affecting type 2 diabetes. The study builds on existing collaborations with local research institutions and physicians. Workshops are offered to the general public and scholars. Educational materials are developed and provided to those affected by type 2 diabetes. Scientist have yet to determine whether, and to what extent, an evolutionary mismatch explains the recent world-wide increase in non-communicable diseases. Using a multipopulational approach, that combines two genome-wide association studies with two evolutionary genomics statistics, this project aims to: (1) comprehensively identify genetic variants associated with type 2 diabetes, (2) test these variants for signatures of past positive selection, and (3) examine whether past positive natural selection affects risk-increasing alleles or protective ones. This gene-by-environment study focuses on a rapidly changing population (i.e., increasingly market-integrated diet and lifestyle). This investigation informs about the portability of the genetic architecture of type 2 diabetes. Examining gene-by-environment interactions reveals the extent to which the genetic effects of type 2 diabetes-associated variants depend on current environmental and lifestyle factors. This project establishes a framework that can be applied to investigations of other mismatch diseases. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.