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.
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.
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis MN, USA. pankow@umn.edu.
Megan D
MD
Fesinmeyer
James B
JB
Meigs
Kari E
KE
North
Fredrick R
FR
Schumacher
Petra
P
Bůžková
Nora
N
Franceschini
Jeffrey
J
Haessler
Robert
R
Goodloe
Kylee L
KL
Spencer
Venkata Saroja
VS
Voruganti
Barbara V
BV
Howard
Rebecca
R
Jackson
Laurence N
LN
Kolonel
Simin
S
Liu
JoAnn E
JE
Manson
Kristine R
KR
Monroe
Kenneth
K
Mukamal
Holli H
HH
Dilks
Sarah A
SA
Pendergrass
Andrew
A
Nato
Peggy
P
Wan
Lynne R
LR
Wilkens
Loic
L
Le Marchand
José Luis
JL
Ambite
Steven
S
Buyske
Jose C
JC
Florez
Dana C
DC
Crawford
Lucia A
LA
Hindorff
Christopher A
CA
Haiman
Ulrike
U
Peters
James S
JS
Pankow
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D023281:Genomics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007328:Insulin / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein