title: Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.
  
  
  METHODS
  Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.
  
  
  RESULTS
  Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.
  
  
  CONCLUSIONS
  A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. anne.hinks@manchester.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Joanna
authors.initials: J
authors.lastname: Cobb
authors.forename: Marc
authors.initials: M
authors.lastname: Sudman
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Edward
authors.initials: E
authors.lastname: Flynn
authors.forename: Jonathon
authors.initials: J
authors.lastname: Packham
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: David N
authors.initials: DN
authors.lastname: Glass
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2