Genetic Risk Assessment of Type 2 Diabetes–Associated Polymorphisms in African Americans

OBJECTIVEdMultiple single nucleotide polymorphisms (SNPs) associated with type 2 di-abetes (T2D) susceptibility have been identified in predominantly European-derived popula-tions. These SNPs have not been extensively investigated for individual and cumulative effects on T2D risk in African Americans. RESEARCH DESIGN ANDMETHODSdSeventeen index T2D risk variants were gen-otyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control sub-jects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes. RESULTSdFrequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs.1, and 5 from ADAMTS9,WFS1,CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P, 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95 % CI 1.01–1.08], P = 0.010; weighted 1.06 [1.03–1.10], P = 8.10 3 1025). When TCF7L