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.

MedStar author(s):
Citation: BMC Medical Genetics. 14:98, 2013.PMID: 24063630Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Research Support, American Recovery and Reinvestment Act | Research Support, N.I.H., Extramural | Research Support, U.S. Gov't, P.H.S.Subject headings: *Blood Glucose/an [Analysis] | *Genome-Wide Association Study | *Insulin/ge [Genetics] | Adaptor Proteins, Signal Transducing/ge [Genetics] | Adult | African Americans/ge [Genetics] | Aged | Alleles | Asian Continental Ancestry Group/ge [Genetics] | Diabetes Mellitus, Type 2/eh [Ethnology] | Diabetes Mellitus, Type 2/ep [Epidemiology] | Diabetes Mellitus, Type 2/ge [Genetics] | European Continental Ancestry Group/ge [Genetics] | Female | Gene Frequency | Genetic Loci | Genomics | Hispanic Americans/ge [Genetics] | Humans | Indians, North American/ge [Genetics] | Insulin/bl [Blood] | Male | Middle Aged | Polymorphism, Single Nucleotide | Transcription Factor 7-Like 2 Protein/ge [Genetics]Local holdings: Available online from MWHC library: 2000 - presentISSN:
  • 1471-2350
Name of journal: BMC medical geneticsAbstract: 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.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.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 x 10-15), versus 3/9 in AA (p= 0.03 to 6 x 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.All authors: Ambite JL, Buyske S, Buzkova P, Crawford DC, Dilks HH, Fesinmeyer MD, Florez JC, Franceschini N, Goodloe R, Haessler J, Haiman CA, Hindorff LA, Howard BV, Jackson R, Kolonel LN, Le Marchand L, Liu S, Manson JE, Meigs JB, Monroe KR, Mukamal K, Nato A, North KE, Pankow JS, Pendergrass SA, Peters U, Schumacher FR, Spencer KL, Voruganti VS, Wan P, Wilkens LRDigital Object Identifier: Date added to catalog: 2014-02-24
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 24063630

Available online from MWHC library: 2000 - present

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.

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.

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 x 10-15), versus 3/9 in AA (p= 0.03 to 6 x 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.

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