Whole blood gene expression and interleukin-6 levels

Honghuang Lin; Roby Joehanes; Luke C Pilling; Josée Dupuis; Kathryn L Lunetta; Sai-Xia Ying; Emelia J Benjamin; Dena Hernandez; Andrew Singleton; David Melzer; Peter J Munson; Daniel Levy; Luigi Ferrucci; Joanne M Murabito

doi:10.1016/j.ygeno.2014.10.003

Whole blood gene expression and interleukin-6 levels

Genomics. 2014 Dec;104(6 Pt B):490-5. doi: 10.1016/j.ygeno.2014.10.003. Epub 2014 Oct 13.

Authors

Affiliations

¹ Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA. Electronic address: hhlin@bu.edu.
² National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institute of Health, Bethesda, MD, USA; Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
³ Epidemiology and Public Health, Medical School, University of Exeter, Exeter EX1 2 LU, UK.
⁴ National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁵ Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institute of Health, Bethesda, MD, USA.
⁶ National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Section of Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
⁷ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁸ National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
⁹ Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA.
¹⁰ National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA; Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: murabito@bu.edu.

Abstract

Background: Circulating interleukin-6 levels increase with advancing age and are a risk factor for various diseases and mortality. The characterization of gene expression profiles associated with interleukin-6 levels might suggest important molecular events underlying its regulation.

Methods and results: We studied the association of transcriptional profiles with interleukin-6 levels in 2422 participants from the Framingham Heart Study Offspring Cohort using Affymetrix Human Exon 1.0 ST Array. We identified 4139 genes that were significantly associated with interleukin-6 levels (FDR<0.05) after adjusting for age, sex and blood cell components. We then replicated 807 genes in the InCHIANTI study with 694 participants. Many of the top genes are involved in inflammation-related pathways or erythrocyte function, including JAK/Stat signaling pathway and interleukin-10 signaling pathway.

Conclusion: We identified and replicated 807 genes that were associated with circulating interleukin-6 levels. Future characterization of interleukin-6 regulation networks may facilitate the identification of additional potential targets for treating inflammation-related diseases.

Keywords: Epidemiology; Gene expression; Inflammation; Interleukin-6.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Profiling
Gene Regulatory Networks*
Humans
Interleukin-6 / blood*
Interleukin-6 / genetics
Signal Transduction
Transcriptome*

Substances

IL6 protein, human
Interleukin-6

Abstract

Publication types

MeSH terms

Substances

Grants and funding