Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

View Abstract

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 non-diabetic participants in the Framingham Heart Study (n=5,056), the Rotterdam Study (n=723), and the InCHIANTI Study (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 Framingham Heart Study and the Rotterdam Study. 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.

Investigators
Abbreviation
Diabetes
Publication Date
2016-09-13
Pubmed ID
27625022
Medium
Print-Electronic
Full Title
Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.
Authors
Chen BH, Hivert MF, Peters MJ, Pilling LC, Hogan JD, Pham LM, Harries LW, Fox CS, Bandinelli S, Dehghan A, Hernandez DG, Hofman A, Hong J, Joehanes R, Johnson AD, Munson PJ, Rybin DV, Singleton AB, Uitterlinden AG, Ying S, Investigators M, Melzer D, Levy D, van Meurs JB, Ferrucci L, Florez JC, Dupuis J, Meigs JB, Kolaczyk ED