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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.

TitleGenetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.
Publication TypeJournal Article
Year of Publication2013
AuthorsFesinmeyer MD, Meigs JB, North KE, Schumacher FR, Bůžková P, Franceschini N, Haessler J, Goodloe R, Spencer KL, Voruganti VSaroja, Howard BV, Jackson R, Kolonel LN, Liu S, Manson JAE, Monroe KR, Mukamal K, Dilks HH, Pendergrass SA, Nato A, Wan P, Wilkens LR, Le Marchand L, Ambite JLuis, Buyske S, Florez JC, Crawford DC, Hindorff LA, Haiman CA, Peters U
Secondary AuthorsPankow JS
JournalBMC Med Genet
Volume14
Pagination98
Date Published2013 Sep 25
ISSN1471-2350
KeywordsAdaptor Proteins, Signal Transducing, Adult, African Americans, Aged, Alleles, Asian Continental Ancestry Group, Blood Glucose, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Genomics, Hispanic Americans, Humans, Indians, North American, Insulin, Male, Middle Aged, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein
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.

DOI10.1186/1471-2350-14-98
Alternate JournalBMC Med Genet
PubMed ID24063630
PubMed Central IDPMC3849560
Grant ListR01 DK078616 / DK / NIDDK NIH HHS / United States
U01CA98758 / CA / NCI NIH HHS / United States
N01-HV-48195 / HV / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
HHSN271201100004C / / PHS HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
U01 HL65521 / HL / NHLBI NIH HHS / United States
HHSN268201100001C / / PHS HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
U01 HG007416 / HG / NHGRI NIH HHS / United States
U01 HL41642 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
AG-15928 / AG / NIA NIH HHS / United States
U01CA136792 / CA / NCI NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
HHSN268201100003C / / PHS HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
HHSN268201100004C / / PHS HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
U01 HL65520, / HL / NHLBI NIH HHS / United States
U01 HL41652 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
U01HG004798-01 / HG / NHGRI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
R37CA54281 / CA / NCI NIH HHS / United States
HHSN268201100046C / / PHS HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
U01HG004801-01 / HG / NHGRI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
HHSN268201100002C / / PHS HHS / United States
P30 CA071789 / CA / NCI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
P01CA33619 / CA / NCI NIH HHS / United States
R01 CA63 / CA / NCI NIH HHS / United States