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Association Analysis in African Americans of European-Derived Type 2 Diabetes Single Nucleotide Polymorphisms From Whole-Genome Association Studies

¹ Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
² Program in Molecular Genetics and Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
³ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina
⁴ Department of Medicine, University of Virginia, Charlottesville, Virginia
⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia
⁶ Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
⁷ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Corresponding author: Donald W. Bowden, dbowden{at}wfubmc.edu

OBJECTIVE— Several whole-genome association studies have reported identification of type 2 diabetes susceptibility genes in various European-derived study populations. Little investigation of these loci has been reported in other ethnic groups, specifically African Americans. Striking differences exist between these populations, suggesting they may not share identical genetic risk factors. Our objective was to examine the influence of type 2 diabetes genes identified in whole-genome association studies in a large African American case-control population.

RESEARCH DESIGN AND METHODS— Single nucleotide polymorphisms (SNPs) in 12 loci (e.g., TCF7L2, IDE/KIF11/HHEX, SLC30A8, CDKAL1, PKN2, IGF2BP2, FLJ39370, and EXT2/ALX4) associated with type 2 diabetes in European-derived populations were genotyped in 993 African American type 2 diabetic and 1,054 African American control subjects. Additionally, 68 ancestry-informative markers were genotyped to account for the impact of admixture on association results.

RESULTS— Little evidence of association was observed between SNPs, with the exception of those in TCF7L2, and type 2 diabetes in African Americans. One TCF7L2 SNP (rs7903146) showed compelling evidence of association with type 2 diabetes (admixture-adjusted additive P [P_a] = 1.59 x 10^–6). Only the intragenic SNP on 11p12 (rs9300039, dominant P [P_d] = 0.029) was also associated with type 2 diabetes after admixture adjustments. Interestingly, four of the SNPs are monomorphic in the Yoruba population of the HAPMAP project, with only the risk allele from the populations of European descent present.

CONCLUSIONS— Results suggest that these variants do not significantly contribute to interindividual susceptibility to type 2 diabetes in African Americans. Consequently, genes contributing to type 2 diabetes in African Americans may, in part, be different from those in European-derived study populations. High frequency of risk alleles in several of these genes may, however, contribute to the increased prevalence of type 2 diabetes in African Americans.

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