The purpose of this project is to locate the genes for and describe the genetic basis of type 2 diabetes, while accounting for environmental risk factors. Type 2 diabetes is a common heterogeneous disorder with evidence for both genetic and environmental causes. However, despite evidence for a strongly inherited component, major susceptibility genes have so far not been found for the more common forms of type 2 diabetes. The investigators propose that incorporating the known influence of environmental factors such as diet and physical activity into analyses will improve the power to measure the association and linkage between genetic markers and diabetes. Recent advances in analytic techniques that allow testing for genetic association and linkage in complex diseases such as type 2 diabetes, while also testing for gene-environment interaction, will make this approach possible.

The proposed study is a family study design. All nuclear families identified from the San Luis Valley Diabetes Study Cohort in which there is at least one affected in a sibship will be studied, with the goal of maximizing the number of families that can be used in transmission-disequilibrium analyses. Approximately 2000 parents and offspring will be genotyped for candidate genes and candidate regions that have been, or will be, discovered through independent genome scans for diabetes genes. Phenotypic and environmental data (e.g., physical activity and dietary histories) will be collected from the offspring. They will use transmission-disequilibrium test methods of analysis on 560 Hispanic and 457 non-Hispanic white "trios" to identify and localize genes associated with type 2 diabetes, while accounting for interactions with diet and physical activity.

R01DK054981

1999-08-20

2004-07-31