We have conducted a GWAS in a Caucasian cohort of juvenile idiopathic arthritis (JIA) patients and have previously published findings limited to autoimmune loci shared with other diseases. The goal of this study was to identify novel JIA predisposing loci using genome-wide approaches.
The Discovery cohort consisted of Caucasian JIA cases (814) and local controls (658) genotyped on the Affymetrix SNP 6.0 Array along with 2400 out-of-study controls. A replication study consisted of 10 SNPs genotyped in 1744 cases and 7010 controls from the US and Europe.
Analysis within the Discovery cohort provided evidence of associations at 3q13 within C3orf1 and near CD80 (rs4688011, OR=1.37, P=1.88×10−6), and 10q21 near the gene JMJD1C [rs6479891, odds ratio (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 continued to provide evidence for association for these 4 SNPs (rs4688011, P=3.6×10−7, rs6479891, P=4.33×10−5; rs12411988, P=2.71×10−5; and rs10995450, 5.39×10−5;). Gene expression data from 68 JIA cases and 23 local controls showed cis eQTL associations for C3orf1 SNP rs4688011 (P=0.024 or P=0.034, depending on probe set) and the JMJD1C SNPs rs6479891 and rs12411988 (P=0.01 and P=0.008, respectively). A variance component liability model estimated that common SNP variation accounts for ~1/3 of JIA susceptibility.
Genetic association results and correlated gene expression findings provide evidence of association at 3q13 and 10q21 for JIA and offer novel genes as plausible candidates in disease pathology.