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Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations

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 th...

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Autores principales: Chen, Brian H., Hivert, Marie-France, Peters, Marjolein J., Pilling, Luke C., Hogan, John D., Pham, Lisa M., Harries, Lorna W., Fox, Caroline S., Bandinelli, Stefania, Dehghan, Abbas, Hernandez, Dena G., Hofman, Albert, Hong, Jaeyoung, Joehanes, Roby, Johnson, Andrew D., Munson, Peter J., Rybin, Denis V., Singleton, Andrew B., Uitterlinden, André G., Ying, Saixia, Melzer, David, Levy, Daniel, van Meurs, Joyce B.J., Ferrucci, Luigi, Florez, Jose C., Dupuis, Josée, Meigs, James B., Kolaczyk, Eric D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127245/
https://www.ncbi.nlm.nih.gov/pubmed/27625022
http://dx.doi.org/10.2337/db16-0470
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author Chen, Brian H.
Hivert, Marie-France
Peters, Marjolein J.
Pilling, Luke C.
Hogan, John D.
Pham, Lisa M.
Harries, Lorna W.
Fox, Caroline S.
Bandinelli, Stefania
Dehghan, Abbas
Hernandez, Dena G.
Hofman, Albert
Hong, Jaeyoung
Joehanes, Roby
Johnson, Andrew D.
Munson, Peter J.
Rybin, Denis V.
Singleton, Andrew B.
Uitterlinden, André G.
Ying, Saixia
Melzer, David
Levy, Daniel
van Meurs, Joyce B.J.
Ferrucci, Luigi
Florez, Jose C.
Dupuis, Josée
Meigs, James B.
Kolaczyk, Eric D.
author_facet Chen, Brian H.
Hivert, Marie-France
Peters, Marjolein J.
Pilling, Luke C.
Hogan, John D.
Pham, Lisa M.
Harries, Lorna W.
Fox, Caroline S.
Bandinelli, Stefania
Dehghan, Abbas
Hernandez, Dena G.
Hofman, Albert
Hong, Jaeyoung
Joehanes, Roby
Johnson, Andrew D.
Munson, Peter J.
Rybin, Denis V.
Singleton, Andrew B.
Uitterlinden, André G.
Ying, Saixia
Melzer, David
Levy, Daniel
van Meurs, Joyce B.J.
Ferrucci, Luigi
Florez, Jose C.
Dupuis, Josée
Meigs, James B.
Kolaczyk, Eric D.
author_sort Chen, Brian H.
collection PubMed
description 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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spelling pubmed-51272452017-12-01 Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations Chen, Brian H. Hivert, Marie-France Peters, Marjolein J. Pilling, Luke C. Hogan, John D. Pham, Lisa M. Harries, Lorna W. Fox, Caroline S. Bandinelli, Stefania Dehghan, Abbas Hernandez, Dena G. Hofman, Albert Hong, Jaeyoung Joehanes, Roby Johnson, Andrew D. Munson, Peter J. Rybin, Denis V. Singleton, Andrew B. Uitterlinden, André G. Ying, Saixia Melzer, David Levy, Daniel van Meurs, Joyce B.J. Ferrucci, Luigi Florez, Jose C. Dupuis, Josée Meigs, James B. Kolaczyk, Eric D. Diabetes Genetics/Genomes/Proteomics/Metabolomics 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. American Diabetes Association 2016-12 2016-09-13 /pmc/articles/PMC5127245/ /pubmed/27625022 http://dx.doi.org/10.2337/db16-0470 Text en © 2016 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Chen, Brian H.
Hivert, Marie-France
Peters, Marjolein J.
Pilling, Luke C.
Hogan, John D.
Pham, Lisa M.
Harries, Lorna W.
Fox, Caroline S.
Bandinelli, Stefania
Dehghan, Abbas
Hernandez, Dena G.
Hofman, Albert
Hong, Jaeyoung
Joehanes, Roby
Johnson, Andrew D.
Munson, Peter J.
Rybin, Denis V.
Singleton, Andrew B.
Uitterlinden, André G.
Ying, Saixia
Melzer, David
Levy, Daniel
van Meurs, Joyce B.J.
Ferrucci, Luigi
Florez, Jose C.
Dupuis, Josée
Meigs, James B.
Kolaczyk, Eric D.
Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title_full Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title_fullStr Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title_full_unstemmed Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title_short Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations
title_sort peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127245/
https://www.ncbi.nlm.nih.gov/pubmed/27625022
http://dx.doi.org/10.2337/db16-0470
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