Grant: Foundation Grant

Common diseases such as obesity affect large number of individuals worldwide. In Canada alone, there are almost 6 million adults who are obese and the disease is the leading cause of type 2 diabetes (T2D). The proportion of men and women that are obese are similar but women are more likely to be extreme obese than men. Instead, men develop T2D at a lower degree of obesity than women. These metabolic conditions are complex in nature meaning the diseases are caused by multiple underlying factors of which only <50% are believed to be heritable. In past years most of these gene regions have been characterized but how they manifest themselves, interact with the environment or differ from pure environmental effects are still not known. With the development of high-throughput DNA sequencing technologies we are now able to screen millions of sites in our genome that are susceptible for not only genetic but also environmental modulation ('epigenetic'). My research program will take advantage of these technology breakthroughs and develop them further as well as apply on multiple cell types form fat and liver tissue from T2D and non-T2D obese men and women. Using these modern tools we will profile environmental marks in the genome of each cell and study how these profiles differ across men and women and disease state and which cell type that is of most importance. This will allow us to characterize factors that distinguish obese T2D from non-T2D obese individuals in a sex-specific way. We will also use fat cells for genetic manipulation to define the cellular outcome of genetic and 'epigenetic' variants associated with obesity and obesity-induced T2D. Finally, the program will measure the combined set of risk variants in large study material of thousands of individuals to assess their ability to predict future outcomes. A significant finding would directly translate into improved health care enabling targeted treatments for the prevention and cure of obesity and T2D.