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Independent replication analysis of genetic loci with previous evidence of association with juvenile idiopathic arthritis

Justine A Ellis1*, Raul A Chavez1, Angela Pezic2, Anne-Louise Ponsonby2, Jonathan D Akikusa34, Roger C Allen34 and Jane E Munro34

Author Affiliations

1 Genes, Environment & Complex Disease, Murdoch Childrens Research Institute, 50 Flemington Rd, Parkville, Vic, 3052, Australia

2 Environmental & Genetic Epidemiology Research, Murdoch Childrens Research Institute, Parkville, Vic, 3052, Australia

3 Arthritis & Rheumatology, Murdoch Childrens Research Institute, Parkville, Vic, 3052, Australia

4 Rheumatology Unit, Department of General Medicine, Royal Children’s Hospital, Parkville, Vic, 3052, Australia

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Pediatric Rheumatology 2013, 11:12  doi:10.1186/1546-0096-11-12

Published: 18 March 2013



Over the last five years, there have been numerous reports of association of juvenile idiopathic arthritis with single nucleotide polymorphisms (SNPs) at various loci outside the major histocompatibility complex (MHC) region. However, the majority of these association findings have been generated using a limited number of international cohorts, and thus there is benefit in further independent replication. To address this, we examined a total of 56 SNPs in 42 non-MHC gene regions previously reported to be associated with JIA, in the ChiLdhood Arthritis Risk factor Identification sTudY (CLARITY), a new Australian collection of cases and healthy child controls.


Genotyping was performed on a total of 324 JIA cases (mean age 9.7 years, 67.3% female) and 568 controls (mean age 7.8 years, 40.7% female). We demonstrated clear evidence for replication of association of JIA with SNPs in or around c12orf30, c3orf1, PTPN22, STAT4, and TRAF1-C5, confirming the involvement of these loci in disease risk. Further, we generated evidence supportive of replication of association of JIA with loci containing AFF3, CD226, MBL2, PSTPIP1, and RANTES (CCL5). These results were robust to sensitivity analyses for ethnicity.


We have provided valuable independent data as to the underlying genetic architecture of this understudied pediatric autoimmune disease, further confirming five loci outside the MHC, and supporting a role for a further five loci in determining disease risk.

Juvenile idiopathic arthritis; Genetic association; Independent replication