Dataset Information

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.

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.

SUBMITTER: Fesinmeyer MD

PROVIDER: S-EPMC3849560 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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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.

Fesinmeyer Megan D MD Meigs James B JB North Kari E KE Schumacher Fredrick R FR Bůžková Petra P Franceschini Nora N Haessler Jeffrey J Goodloe Robert R Spencer Kylee L KL Voruganti Venkata Saroja VS Howard Barbara V BV Jackson Rebecca R Kolonel Laurence N LN Liu Simin S Manson JoAnn E JE Monroe Kristine R KR Mukamal Kenneth K Dilks Holli H HH Pendergrass Sarah A SA Nato Andrew A Wan Peggy P Wilkens Lynne R LR Le Marchand Loic L Ambite José Luis JL Buyske Steven S Florez Jose C JC Crawford Dana C DC Hindorff Lucia A LA Haiman Christopher A CA Peters Ulrike U Pankow James S JS

BMC medical genetics 20130925

<h4>Background</h4>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.<h4>Methods</h4>As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 ...[more]

PMID: 24063630

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Project description:<p>By relating hundreds of thousands of genotypes to only a few phenotypes, mostly in individuals of one ancestry, genome-wide association (GWA) studies are identifying a rapidly growing number of associations. The Population Architecture using Genomics and Epidemiology (PAGE) Study is designed to further characterize the most promising variants along an epidemiological dimension that is substantial in its sample size, ethnic diversity, breadth of phenotypes, and exposures. PAGE includes scientists and population samples from large ongoing cohort studies: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, CHS, HCHS/SOL, Strong Heart Cohort Study, Strong Heart Family Study), EAGLE (Epidemiologic Architecture for Genes Linked to Environment, based on 3 National Health and Nutrition Examination Surveys (NHANES), MEC (Multiethnic Cohort) and WHI (Women's Health Initiative), with logistical and scientific support contributed by a Coordinating Center and the NHGRI Office of Population Genomics. These studies combined include over 270,000 participants, and populations represented include Asian Americans, African Americans, European Americans, Hispanic Americans, Native Hawaiians and American Indians. Health outcomes and traits of interest are prioritized, followed by replication of trait-genotype associations and generalization of their effects across population groups and environmental contexts. </p> <p>The first phase of genotyping focused on 901 high-profile SNPs having replicated associations with phenotypes related to diabetes, obesity, cardiovascular disease, lipids, cancers, menopause/menarche, inflammation and autoimmunity that are being genotyped in over 121,000 participants, as available for trait-specific analyses. SNP genotyping, quality control and population-specific association analyses are performed within each cohort, followed by meta-analyses using harmonized phenotypes and standardized analytic methods.</p> <p>The second phase of genotyping will be done using the Metabochip. The Metabochip is a custom large-scale (~200K SNPs) Illumina chip designed for association testing of several metabolic-related phenotypes. Genotyping will be performed at each study site and centralized analysis will be managed through the coordinating center.</p> <p>PAGE is generating 3 types of data: tier 1 (minimally curated phenotypes and analyses, all SNPs by all available phenotypes, used for Phenome-wide association study (PheWAS analysis)), tier 2 (carefully curated analyses of phenotypes available at only one of the four PAGE sites) and tier 3 (carefully curated phenotypes for multi-site analyses, data specifically generated for manuscripts). All tiers of data are submitted to the CC, where they undergo QC prior to submission to dbGaP.</p>

Dataset Information

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.

Publications

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.

Similar Datasets

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