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Diabetes Publish Ahead of Print published online ahead of print April 28, 2008
DOI: 10.2337/db07-1319
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Original Research

Association Analysis of European-Derived Type 2 Diabetes SNPs from Whole Genome Association Studies in African Americans

Joshua P. Lewis1,,2, Nicholette D. Palmer1,,3, Pamela J. Hicks1,,3, Michele M. Sale4,,5, Carl D. Langefeld6, Barry I. Freedman7, Jasmin Divers6, and Donald W. Bowden1,,3,,7

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

Objective: Several whole genome association (WGA) studies have reported identification of type 2 diabetes mellitus (T2DM) susceptibility genes in various European-derived populations. Little investigation of these loci has been reported in other ethnic groups, specifically African Americans (AAs). Striking differences exist between these populations, suggesting they may not share identical genetic risk factors. Our objective was to examine the influence of T2DM genes identified in WGA studies in a large AA case-control population.

Research Design and Methods: SNPs in 12 loci (e.g. TCF7L2, IDE/KIF11/HHEX, SLC30A8, CDKAL1, PKN2, IGF2BP2, FLJ39370, and EXT2/ALX4) associated with T2DM in European-derived populations were genotyped in 993 T2DM AA cases and 1054 AA controls. Additionally, 68 ancestry-informative markers (AIMs) were genotyped to account for the impact of admixture on association results.

Results: Except for TCF7L2, little evidence of association was observed between SNPs and T2DM in AAs. One TCF7L2 SNP (rs7903146) showed compelling evidence of association with T2DM (admixture adjusted Pa=1.59x10–6). Only the intragenic SNP on 11p12 (rs9300039, Pd=0.029) was also associated with T2DM after admixture adjustments. Interestingly, 4 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 these variants do not significantly contribute to inter-individual susceptibility to T2DM in AAs. Consequently, genes contributing to T2DM in AAs may, in part, be different from those in European-derived populations. High frequency of risk alleles in several of these genes may, however, contribute to the increased prevalence of T2DM in AAs.

Correspondence: dbowden{at}wfubmc.edu


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