TY - JOUR
T1 - Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations
AU - Chen, Brian H.
AU - Hivert, Marie France
AU - Peters, Marjolein J.
AU - Pilling, Luke C.
AU - Hogan, John D.
AU - Pham, Lisa M.
AU - Harries, Lorna W.
AU - Fox, Caroline S.
AU - Bandinelli, Stefania
AU - Dehghan, Abbas
AU - Hernandez, Dena G.
AU - Hofman, Albert
AU - Hong, Jaeyoung
AU - Joehanes, Roby
AU - Johnson, Andrew D.
AU - Munson, Peter J.
AU - Rybin, Denis V.
AU - Singleton, Andrew B.
AU - Uitterlinden, André G.
AU - Ying, Saixia
AU - Melzer, David
AU - Levy, Daniel
AU - Van Meurs, Joyce B J
AU - Ferrucci, Luigi
AU - Florez, Jose C.
AU - Dupuis, Josée
AU - Meigs, James B.
AU - Kolaczyk, Eric D.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-Associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-Analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.
AB - Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-Associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-Analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.
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U2 - 10.2337/db16-0470
DO - 10.2337/db16-0470
M3 - Article
C2 - 27625022
AN - SCOPUS:85000786872
VL - 65
SP - 3794
EP - 3804
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 12
ER -