Evaluation of genome-wide association study-identified type 2 diabetes loci in African Americans

Am J Epidemiol. 2012 Dec 1;176(11):995-1001. doi: 10.1093/aje/kws176. Epub 2012 Nov 9.

Abstract

Type 2 diabetes (T2D) is up to twice as prevalent among African Americans as Caucasians. Recent genome-wide association studies (GWAS) have identified multiple common genetic risk variants for T2D; however, none of these studies were conducted exclusively among subjects of African ancestry. Investigating these known loci in other populations would be an expedient way to evaluate the generalizability of the current findings. The authors evaluated 29 known T2D loci in a large southeastern US cohort study including 4,288 African Americans (1,554 cases and 2,734 controls) enrolled during 2002-2009. Seven of the 29 single nucleotide polymorphisms (SNPs) examined were found to be associated with T2D risk at P ≤ 0.05, including rs6769511 (IGF2BP2), 2 SNPs in the WFS1 gene (rs4689388 and rs1801214), rs7903146 (TCF7L2), and 3 SNPs in the KCNQ1 gene (rs231362, rs2237892, and rs2237897). Notably, the association for rs7903146 reached the GWAS significance level (P = 3.6 × 10(-8)), with an odds ratio per T allele of 1.32 (95% confidence interval: 1.20, 1.46). Regional analyses using GWAS data from Vanderbilt University's BioVU DNA biobank showed significant associations (P < 0.05) with 9 loci, though no association was observed for the index SNPs reported in European- or Asian-ancestry populations. These results extend some of the recent GWAS findings to African Americans and may guide future efforts to identify causal variants for T2D.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • African Americans / genetics*
  • Aged
  • Alleles
  • Body Mass Index
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / classification
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Logistic Models
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Principal Component Analysis
  • Prospective Studies
  • RNA-Binding Proteins / genetics
  • Risk Assessment
  • Risk Factors
  • Transcription Factor 7-Like 2 Protein / genetics
  • United States / epidemiology

Substances

  • IGF2BP2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • wolframin protein