A genome-wide association search for type 2 diabetes genes in african americans

DIAGRAM Consortium, MAGIC Investigators, Nicholette D. Palmer, Caitrin W. McDonough, Pamela J. Hicks, Bong H. Roh, Maria R. Wing, S. Sandy An, Jessica M. Hester, Jessica N. Cooke, Meredith A. Bostrom, Megan E. Rudock, Matthew E. Talbert, Joshua P. Lewis, Assiamira Ferrara, Lingyi Lu, Julie T. Ziegler, Michele M. Sale, Jasmin Divers, Daniel ShrinerAdebowale Adeyemo, Charles N. Rotimi, Maggie C.Y. Ng, Carl D. Langefeld, Barry I. Freedman, Donald W. Bowden

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138 Citations (Scopus)


African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P-8). SNP rs7560163 (P = 7.0×10-9, OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P-5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Original languageEnglish
Article numbere29202
JournalPLoS One
Issue number1
Publication statusPublished - 4 Jan 2012


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