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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK054981-01A1
Application #
2900351
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Mckeon, Catherine T
Project Start
1999-08-20
Project End
2003-07-31
Budget Start
1999-08-20
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Nelson, Tracy L; Fingerlin, Tasha E; Moss, Laurie K et al. (2007) Association of the peroxisome proliferator-activated receptor gamma gene with type 2 diabetes mellitus varies by physical activity among non-Hispanic whites from Colorado. Metabolism 56:388-93
Nelson, Tracy L; Fingerlin, Tasha E; Moss, Laurie et al. (2007) The PPARgamma Pro12Ala polymorphism is not associated with body mass index or waist circumference among Hispanics from Colorado. Ann Nutr Metab 51:252-7
Nelson, T L; Fingerlin, T E; Moss, L et al. (2007) The peroxisome proliferator-activated receptor gamma coactivator-1 alpha gene (PGC-1alpha) is not associated with type 2 diabetes mellitus or body mass index among Hispanic and non Hispanic Whites from Colorado. Exp Clin Endocrinol Diabetes 115:268-75
Schneider, A; Lawrence, E C; Barmada, M M et al. (2005) The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA. Diabet Med 22:744-8
James, Katherine; Weitzel, Lindsay-Rae B; Engelman, Corinne D et al. (2003) Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study. BMC Genet 4 Suppl 1:S83
Selinger-Leneman, Hana; Genin, Emmanuelle; Norris, Jill M et al. (2003) Does accounting for gene-environment (GxE) interaction increase the power to detect the effect of a gene in a multifactorial disease? Genet Epidemiol 24:200-7
Engelman, Corinne D; Brady, Heather L; Baron, Anna E et al. (2003) Comparison between two analytic strategies to detect linkage to obesity with genetically determined age of onset: the Framingham Heart Study. BMC Genet 4 Suppl 1:S90
Norris, J M; Selinger-Leneman, H; Genin, E (2001) Investigation of a candidate gene, environment, and G x E interaction using case-control and case-parent study designs. Genet Epidemiol 21 Suppl 1:S843-8