Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis

Nat Genet. 2013 Jun;45(6):664-9. doi: 10.1038/ng.2614. Epub 2013 Apr 21.


We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Juvenile / genetics*
  • Arthritis, Juvenile / immunology
  • Case-Control Studies
  • Child
  • Chromosome Mapping
  • Gene Frequency
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Interleukins / genetics
  • Linkage Disequilibrium
  • Molecular Sequence Annotation
  • Polymorphism, Single Nucleotide
  • Receptors, CCR / genetics
  • Receptors, Interleukin / genetics
  • Risk Factors


  • Interleukins
  • Receptors, CCR
  • Receptors, Interleukin

Grants and funding