title: Independent confirmation of juvenile idiopathic arthritis genetic risk loci previously identified by immunochip array analysis.
abstract: BACKGROUND
  Our understanding of the genetic factors underlying juvenile idiopathic arthritis (JIA) is growing, but remains incomplete. Recently, a number of novel genetic loci were reported to be associated with JIA at (or near) genome-wide significance in a large case-control discovery sample using the Immunochip genotyping array. However, independent replication of findings has yet to be performed. We therefore attempted to replicate these newly identified loci in the Australian CLARITY JIA case-control sample.
  
  
  RESULTS
  Genotyping was successfully performed on a total of 404 JIA cases (mean age 6.4 years, 68% female) and 676 healthy child controls (mean age 7.1 years, 42% female) across 19 SNPs previously associated with JIA. We replicated a significant association (p < 0.05, odds ratio (OR) in a direction consistent with the previous report) for seven loci, six replicated for the first time--C5orf56-IRF1 (rs4705862), ERAP2-LNPEP (rs27290), PRR5L (rs4755450), RUNX1 (rs9979383), RUNX3 (rs4648881), and UBE2L3 (rs2266959).
  
  
  CONCLUSIONS
  We have carried out the first independent replication of association for six genes implicated in JIA susceptibility. Our data significantly strengthens the evidence that these loci harbor true disease associated variants. Thus, this study makes an important contribution to the growing body of international data that is revealing the genetic risk landscape of JIA.
authors.affiliation: Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Department of Paediatrics, The University of Melbourne, Parkville, Vic 3010 Australia.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Chiaroni-Clarke
authors.affiliation: Arthritis & Rheumatology, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Paediatric Rheumatology Unit, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052 Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Munro
authors.affiliation: Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Department of Paediatrics, The University of Melbourne, Parkville, Vic 3010 Australia.
authors.forename: Raul A
authors.initials: RA
authors.lastname: Chavez
authors.affiliation: Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Pezic
authors.affiliation: Arthritis & Rheumatology, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Paediatric Rheumatology Unit, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052 Australia.
authors.forename: Roger C
authors.initials: RC
authors.lastname: Allen
authors.affiliation: Arthritis & Rheumatology, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Paediatric Rheumatology Unit, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052 Australia.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Akikusa
authors.affiliation: Paediatric Rheumatology Department, Monash Children's Hospital, Monash Medical Centre, 246 Clayton Road, Clayton, Vic 3168 Australia.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Piper
authors.affiliation: Cancer & Disease Epigenetics, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Department of Paediatrics, The University of Melbourne, Parkville, Vic 3010 Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Department of Paediatrics, The University of Melbourne, Parkville, Vic 3010 Australia.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Ponsonby
authors.affiliation: Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Victoria 3052 Australia ; Department of Paediatrics, The University of Melbourne, Parkville, Vic 3010 Australia.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Ellis
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D002352:Carrier Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D047908:Intracellular Signaling Peptides and Proteins; C570157:Protor-2 protein, human; C493728:RUNX1 protein, human; C493729:Runx3 protein, human
keywords: Genetic association; Immunochip; Independent replication; Juvenile idiopathic arthritis