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

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), versus 3/9 in AA (p= 0.03 to 6 × 10), 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. * Correspondence: pankow@umn.edu Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis MN, USA Full list of author information is available at the end of the article © 2013 Fesinmeyer et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fesinmeyer et al. BMC Medical Genetics 2013, 14:98 Page 2 of 8 http://www.biomedcentral. com/1471-2350/14/98 Background Impaired glucose homeostasis is associated with increased risk of cardiovascular disease and type 2 diabetes [1,2]. While plasma glucose and insulin concentrations normally fluctuate in response to dietary intake and physical activity levels, several genomewide association studies (GWAS) have demonstrated that common genetic variants contribute to glucose homeostasis. Most studies of this complex trait have focused on primarily ancestrally European populations, despite the high prevalence of insulin resistance and diabetes in many minority groups. Investigation of the clinical and public health implications of these genetic discoveries requires not only confirmation in EA populations, but importantly generalization of these associations to other groups such as African Americans, Hispanics, American Indians, and Asians; groups that were not adequately represented in most GWAS. A prior study found that a genetic risk score composed of 16 SNPs previously associated with fasting glucose in GWAS in European populations was associated with fasting glucose in non-Hispanic blacks and Mexican Americans, indicating that genetic factors associated with fasting glucose may be shared across some racial/ethnic groups [3]. The purpose of this study is to examine 36,579 participants from diverse racial and ethnic backgrounds as part of the NHGRI-supported ‘Population Architecture using Genomics and Epidemiology (PAGE)’ Consortium to investigate associations between SNPs previously-identified in genome-wide scans for loci associated with glucose and insulin concentrations.