title: Whole blood gene expression and interleukin-6 levels.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Honghuang
authors.initials: H
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Roby
authors.initials: R
authors.lastname: Joehanes
authors.affiliation: Epidemiology and Public Health, Medical School, University of Exeter, Exeter EX1 2 LU, UK.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pilling
authors.affiliation: 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.
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: 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.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institute of Health, Bethesda, MD, USA.
authors.forename: Sai-Xia
authors.initials: SX
authors.lastname: Ying
authors.affiliation: 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.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Epidemiology and Public Health, Medical School, University of Exeter, Exeter EX1 2 LU, UK.
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.affiliation: 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.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: 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.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
mesh_terms: D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Epidemiology; Gene expression; Inflammation; Interleukin-6