Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations

Brian H. Chen, Marie France Hivert, Marjolein J. Peters, Luke C. Pilling, John D. Hogan, Lisa M. Pham, Lorna W. Harries, Caroline S. Fox, Stefania Bandinelli, Abbas Dehghan, Dena G. Hernandez, Albert Hofman, Jaeyoung Hong, Roby Joehanes, Andrew D. Johnson, Peter J. Munson, Denis V. Rybin, Andrew B. Singleton, André G. Uitterlinden, Saixia YingDavid Melzer, Daniel Levy, Joyce B J Van Meurs, Luigi Ferrucci, Jose C. Florez, Josée Dupuis, James B. Meigs, Eric D. Kolaczyk

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)3794-3804
Number of pages11
JournalDiabetes
Volume65
Issue number12
DOIs
Publication statusPublished - Dec 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chen, B. H., Hivert, M. F., Peters, M. J., Pilling, L. C., Hogan, J. D., Pham, L. M., ... Kolaczyk, E. D. (2016). Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations. Diabetes, 65(12), 3794-3804. https://doi.org/10.2337/db16-0470