TY - JOUR T1 - 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. JF - BMC Med Genet Y1 - 2013 A1 - Fesinmeyer, Megan D A1 - Meigs, James B A1 - North, Kari E A1 - Schumacher, Fredrick R A1 - Bůzková, Petra A1 - Franceschini, Nora A1 - Haessler, Jeffrey A1 - Goodloe, Robert A1 - Spencer, Kylee L A1 - Voruganti, Venkata Saroja A1 - Howard, Barbara V A1 - Jackson, Rebecca A1 - Kolonel, Laurence N A1 - Liu, Simin A1 - Manson, JoAnn E A1 - Monroe, Kristine R A1 - Mukamal, Kenneth A1 - Dilks, Holli H A1 - Pendergrass, Sarah A A1 - Nato, Andrew A1 - Wan, Peggy A1 - Wilkens, Lynne R A1 - Le Marchand, Loïc A1 - Ambite, Jose Luis A1 - Buyske, Steven A1 - Florez, Jose C A1 - Crawford, Dana C A1 - Hindorff, Lucia A A1 - Haiman, Christopher A A1 - Peters, Ulrike A1 - Pankow, James S KW - Adaptor Proteins, Signal Transducing KW - Adult KW - African Americans KW - Aged KW - Alleles KW - Asian Continental Ancestry Group KW - Blood Glucose KW - Diabetes Mellitus, Type 2 KW - European Continental Ancestry Group KW - Female KW - Gene Frequency KW - Genetic Loci KW - Genome-Wide Association Study KW - Genomics KW - Hispanic Americans KW - Humans KW - Indians, North American KW - Insulin KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Transcription Factor 7-Like 2 Protein AB -

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.

VL - 14 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24063630?dopt=Abstract ER -