Grant: Catalyst Grant: Environments, Genes and Chronic Disease - Diabesity

Metabolic syndrome (MetS) is a group of metabolic conditions that occur together in a given individual and that increases the risk of developing type 2 diabetes and cardiovascular disease (CVD). These risk factors include central obesity, abnormal lipid levels, raised fasting glucose levels and elevated blood pressure. The MetS represents a good chronic disease model for the study of gene-environment interaction because there is considerable evidence showing that 1) MetS and it's underlying risk factors are heritable and 2) nutrients, especially dietary fat, and physical inactivity are important modifiable risk factors that can modify the development of MetS. High estimates of heritability (30-80%) have been reported for the various components of the MetS, but the large number of genes that have been found to be associated with MetS so far typically confer a small increase in the risk of MetS. One explanation for this phenomenon is failure to take into account gene-environment interaction, which means that lifestyle factors like nutrition and physical activity can modify the effects of identified genes resulting in higher effects on risk of MetS in subsets of exposed individuals. The objective of this proposal is to investigate the modifying effects of nutritional and physical activity exposures on MetS susceptibility genes and to develop valid estimates of genetic and exposure effects sizes using powerful statistical methods to better characterize gene-environment interaction. Data generated by this research will increase our understanding of how the association between genetic and environmental determinants of MetS are modulated by each other and will help explain the interplay beteween genes and environment in MetS and lead to interventions targeted to genetically vulnerable subjects to improve their diet and/or physical activity level.