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Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children

DOI: 10.1186/1479-7364-5-2-79

Keywords: insulin sensitivity, genetic admixture, type 2 diabetes, genetic association, ancestry-informative marker

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Abstract:

Type 2 diabetes prevalence in the paediatric population is increasing, while age at onset is decreasing [1,2]. Type 2 diabetes also disproportionately affects racial/ethnic minorities in the USA [3]. Twin and familial studies have shown a substantial genetic component to the disease, as well as its related phenotypes [4-10]. Although much is known about environmental contributions to type 2 diabetes, only a very small proportion of the variation due to genetic factors is currently explainable by identified genetic polymorphisms [11-13]. Similarly, little is known about the specific genetic factors that may contribute to population differences in diabetes prevalence. Because the origins of type 2 diabetes are likely to be rooted in childhood, a better understanding of genetic determinants among paediatric populations could lead to a better insight into the aetiology of type 2 diabetes and eventually improved prediction and prevention of the disease.Endo-phenotypes can be useful in closely dissecting the genetic basis of eventual disease status [14]. For type 2 diabetes, several such measurable phenotypes exist, typically examining measures of glucose and insulin homeostasis. These measures serve as indicators of reduced insulin response and action that may presage type 2 diabetes [15,16]. Furthermore, previous studies have suggested a genetic basis for racial/ethnic differences in insulin dynamics [17,18]. Examining the genetic basis for these detailed phenotypes therefore allows for a much better understanding of the link between the genetic and metabolic pathways that underlie the development of type 2 diabetes.Since the loci recently identified by genome-wide association studies (GWAS)[19-21] occurred predominantly among individuals of European descent, there is considerable uncertainty as to whether these associations translate to other populations. Hispanic Americans (HAs) and African Americans (AAs) suffer from higher rates of type 2 diabetes than European Amer

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