Location: Boston, Massachusetts
Project Number: 8050-51000-077-01-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Mar 20, 2009
End Date: Mar 19, 2014
1. Identify new human genes involved in the homeostasis of lipid metabolism using genome-wide association studies and bioinformatics. 2. Identify candidate genes for overweight and obesity in humans with special emphasis on those modulating the risk for the metabolic syndrome. 3. Identify genetic factors determining differential susceptibility towards chronic disorders in response to a Western-type diet and lifestyle in humans with differing ethnic backgrounds. 4. Identify new longevity genes and describe their modulation by nutritional and environmental factors in animals and humans.
Because the predisposition to most common ailments affecting healthy aging and the responses of the individual to nutrients both contain a strong genetic component, our approach aims to uncover sets of genes involved in the predisposition to alterations in fasting and non fasting lipid metabolism and obesity and dietary response and to describe specific gene-diet interactions. This will be tested, using high throughput genotyping techniques, both in ongoing studies of free-living populations from different ethnic groups and in the metabolic ward (intervention studies). Our primary focus is to describe gene-diet interactions affecting/influencing progression of the metabolic syndrome, in particular obesity and dyslipidemia, often precursors to cardiovascular disease and diabetes. Cardiovascular candidate genes, both those previously described in the literature as well as those we identify through new genetic technologies and bioinformatics analysis will be used to examine associations and interactions on various scales. These include genetic variations, disease-related phenotypes and specific nutrients [fatty acids, cholesterol, fiber) and behavioral habits (alcohol consumption, smoking, physical (in-activity]. Rigorous statistical analysis will uncover the associations between phenotypes indicative of increased risk of metabolic syndrome and the genes responsible for such. Because cardiovascular disease and diabetes are traditionally considered diseases of the aged, we will also continue with our investigations to identify genes responsible for healthy aging. The principal approach taken for these studies involves gene expression microarray in silico analysis of animal models of aging and longevity. Candidate aging genes will then be studied in human populations.