Independent confirmation of juvenile idiopathic arthritis genetic risk loci previously identified by immunochip array analysis.
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.


FINDINGS
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.
['Chiaroni-Clarke|Rachel C|RC|', 'Munro|Jane E|JE|', 'Chavez|Raul A|RA|', 'Pezic|Angela|A|', 'Allen|Roger C|RC|', 'Akikusa|Jonathan D|JD|', 'Piper|Susan E|SE|', 'Saffery|Richard|R|', 'Ponsonby|Anne-Louise|AL|', 'Ellis|Justine A|JA|']
D001171:Arthritis, Juvenile D002352:Carrier Proteins D016022:Case-Control Studies D002648:Child D050676:Core Binding Factor Alpha 2 Subunit D050677:Core Binding Factor Alpha 3 Subunit D005260:Female D056426:Genetic Loci D020022:Genetic Predisposition to Disease D005838:Genotype D006801:Humans D007118:Immunoassay D050856:Interferon Regulatory Factor-1 D047908:Intracellular Signaling Peptides and Proteins D008297:Male D020411:Oligonucleotide Array Sequence Analysis D020641:Polymorphism, Single Nucleotide D012307:Risk Factors
Juvenile idiopathic arthritis Immunochip Independent replication Genetic association