title: Role of Established Type 2 Diabetes-Susceptibility Genetic Variants in a High Prevalence American Indian Population.
abstract: Several single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM) have been identified, but there is little information on their role in populations at high risk for T2DM. We genotyped SNPs at 63 T2DM loci in 3,421 individuals from a high-risk American Indian population. Nominally significant (P < 0.05) associations were observed at nine SNPs in a direction consistent with the established association. A genetic risk score derived from all loci was strongly associated with T2DM (odds ratio 1.05 per risk allele, P = 6.2 × 10(-6)) and, in 292 nondiabetic individuals, with lower insulin secretion (by 4% per copy, P = 4.1 × 10(-6)). Genetic distances between American Indians and HapMap populations at T2DM markers did not differ significantly from genomic expectations. Analysis of U.S. national survey data suggested that 66% of the difference in T2DM prevalence between African Americans and European Americans, but none of the difference between American Indians and European Americans, was attributable to allele frequency differences at these loci. These analyses suggest that, in general, established T2DM loci influence T2DM in American Indians and that risk is mediated in part through an effect on insulin secretion. However, differences in allele frequencies do not account for the high population prevalence of T2DM.
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ rhanson@phx.niddk.nih.gov.
authors: Robert L
authors: RL
authors: Hanson
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Rong
authors: R
authors: Rong
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Sayuko
authors: S
authors: Kobes
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Yunhua Li
authors: YL
authors: Muller
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: E Jennifer
authors: EJ
authors: Weil
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Jeffrey M
authors: JM
authors: Curtis
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Robert G
authors: RG
authors: Nelson
authors: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
authors: Leslie J
authors: LJ
authors: Baier
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk