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| Genetic and Epigenetic Studies of Type 2 Diabetes in American Indians | ||||||||
| Robert L. Hanson, MD, MPH | ||||||||
| Staff Scientist, Diabetes and Arthritis Epidemiology Section NIDDK, National Institutes of Health |
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Type 2 diabetes is a complex disease in which genetic and epigenetic factors are likely to play a role. Our group has been studying the genetic epidemiology of type 2 diabetes and related traits in American Indians. In this population, there is a strong effect of the intrauterine environment in that individuals who are born to a diabetic mother have a high risk of developing diabetes and obesity later in life, independent of the risk conferred by genetics. Diabetes is also strongly familial, regardless of exposure to hyperglycemia in utero, and this suggests an effect of genetics independent of the intrauterine environment. To identify specific variants that increase the risk of type 2 diabetes and its risk factors in this population, genome-wide linkage and association mapping studies are being conducted and candidate genes are being evaluated. Many of the variants identified in European populations as associated with type 2 diabetes appear to be modestly associated in American Indians as well; however, some variants (such as the common those in TCF7L2) have significantly weaker effects in American Indians than in Europeans. Parent-of-origin effects and interaction with the diabetic intrauterine environment may be important modifiers of the genetic risk in this population. Linkage analysis that accounts for parent-of-origin effects has identified a potential locus for birth weight on chromosome 11. These effects may, in part, describe the different effects of maternal and paternal diabetes observed for birth weight in this population.
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| Dr Hanson has been with the Diabetes and Arthritis Epidemiology Section since 1991. The work of the section has focused on the risk factors for type 2 diabetes mellitus and its complications (especially diabetic nephropathy and retinopathy), obesity and its relationship to diabetes, diagnostic criteria for diabetes, and on statistical methods in genetic epidemiology. Recently Dr Hanson’s work has focused on the application of statistical genetic techniques to facilitate the identification of susceptibility genes for diabetes, obesity and diabetic complications. He is also involved in classical epidemiologic studies of risk factors for diabetes and its complications, the Diabetes Prevention Program, a clinical trial in prevention of type 2 diabetes and the Family Investigation of Nephropathy and Diabetes, a genetics study. | ||||||||
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