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Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study

  • Author(s): Fesinmeyer, Megan D;
  • Meigs, James B;
  • North, Kari E;
  • Schumacher, Fredrick R;
  • Bůžková, Petra;
  • Franceschini, Nora;
  • Haessler, Jeffrey;
  • Goodloe, Robert;
  • Spencer, Kylee L;
  • Voruganti, Venkata;
  • Howard, Barbara V;
  • Jackson, Rebecca;
  • Kolonel, Laurence N;
  • Liu, Simin;
  • Manson, JoAnn E;
  • Monroe, Kristine R;
  • Mukamal, Kenneth;
  • Dilks, Holli H;
  • Pendergrass, Sarah A;
  • Nato, Andrew;
  • Wan, Peggy;
  • Wilkens, Lynne R;
  • Marchand, Loic;
  • Ambite, José;
  • Buyske, Steven;
  • Florez, Jose C;
  • Crawford, Dana C;
  • Hindorff, Lucia A;
  • Haiman, Christopher A;
  • Peters, Ulrike;
  • Pankow, James S
  • et al.

Abstract Background Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. Methods As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Results Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Conclusions Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.

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