title: Associations between joint effusion in the knee and gene expression levels in the circulation: a meta-analysis.
abstract: OBJECTIVE
  To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation.
  
  
  METHODS
  Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools.
  
  
  RESULTS
  In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways.
  
  
  CONCLUSIONS
  Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage.
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Marjolein J
authors.initials: MJ
authors.lastname: Peters
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Yolande F M
authors.initials: YF
authors.lastname: Ramos
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: den Hollander
authors.affiliation: Department of General Practice, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Dieuwke
authors.initials: D
authors.lastname: Schiphof
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors.forename: Edwin H G
authors.initials: EH
authors.lastname: Oei
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Clinical Epidemiology and Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: Kloppenburg
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Johan L
authors.initials: JL
authors.lastname: Bloem
authors.affiliation: Department of General Practice, Erasmus MC, Rotterdam, Netherlands; Department of Orthopedics, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Sita M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
keywords: blood; inflammation; joint effusion; knee osteoarthritis; molecular markers