title: Genome-wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13.
abstract: OBJECTIVE
  In a genome-wide association study of Caucasian patients with juvenile idiopathic arthritis (JIA), we have previously described findings limited to autoimmunity loci shared by JIA and other diseases. The present study was undertaken to identify novel JIA-predisposing loci using genome-wide approaches.
  
  
  METHODS
  The discovery cohort consisted of Caucasian JIA cases (n = 814) and local controls (n = 658) genotyped on the Affymetrix Genome-Wide SNP 6.0 Array, along with 2,400 out-of-study controls. In a replication study, we genotyped 10 single-nucleotide polymorphisms (SNPs) in 1,744 cases and 7,010 controls from the US and Europe.
  
  
  RESULTS
  Analysis within the discovery cohort provided evidence of associations at 3q13 within C3orf1 and near CD80 (rs4688011) (odds ratio [OR] 1.37, P = 1.88 × 10(-6) ) and at 10q21 near JMJD1C (rs647989 [OR 1.59, P = 6.1 × 10(-8) ], rs12411988 [OR 1.57, P = 1.16 × 10(-7) ], and rs10995450 [OR 1.31, P = 6.74 × 10(-5) ]). Meta-analysis provided further evidence of association for these 4 SNPs (P = 3.6 × 10(-7)  for rs4688011, P = 4.33 × 10(-5)  for rs6479891, P = 2.71 × 10(-5)  for rs12411988, and P = 5.39 × 10(-5)  for rs10995450). Gene expression data on 68 JIA cases and 23 local controls showed cis expression quantitative trait locus associations for C3orf1 SNP rs4688011 (P = 0.024 or P = 0.034, depending on the probe set) and JMJD1C SNPs rs6479891 and rs12411988 (P = 0.01 or P = 0.04, depending on the probe set and P = 0.008, respectively). Using a variance component liability model, it was estimated that common SNP variation accounts for approximately one-third of JIA susceptibility.
  
  
  CONCLUSIONS
  Genetic association results and correlated gene expression findings provide evidence of JIA association at 3q13 and suggest novel genes as plausible candidates in disease pathology.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Susan.thompson@cchmc.org
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Marion
authors.forename: Marc
authors.initials: M
authors.lastname: Sudman
authors.forename: Mary
authors.initials: M
authors.lastname: Ryan
authors.forename: Monica
authors.initials: M
authors.lastname: Tsoras
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.forename: Michael G
authors.initials: MG
authors.lastname: Barnes
authors.forename: Paula S
authors.initials: PS
authors.lastname: Ramos
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Haas
authors.forename: Sampath
authors.initials: S
authors.lastname: Prahalad
authors.forename: John F
authors.initials: JF
authors.lastname: Bohnsack
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wise
authors.forename: Marilynn
authors.initials: M
authors.lastname: Punaro
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Rosé
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Pajewski
authors.forename: Michael
authors.initials: M
authors.lastname: Spigarelli
authors.forename: Mehdi
authors.initials: M
authors.lastname: Keddache
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: David N
authors.initials: DN
authors.lastname: Glass
mesh_terms: D001171:Arthritis, Juvenile / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000208:ethnology