Literature DB >> 22354554

Genome-wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13.

Susan D Thompson1, Miranda C Marion, Marc Sudman, Mary Ryan, Monica Tsoras, Timothy D Howard, Michael G Barnes, Paula S Ramos, Wendy Thomson, Anne Hinks, Johannes-Peter Haas, Sampath Prahalad, John F Bohnsack, Carol A Wise, Marilynn Punaro, Carlos D Rosé, Nicholas M Pajewski, Michael Spigarelli, Mehdi Keddache, Michael Wagner, Carl D Langefeld, David N Glass.   

Abstract

OBJECTIVE: In a genome-wide association study of Caucasian patients with juvenile idiopathic arthritis (JIA), we have previously described findings limited to autoimmunity loci shared by JIA and other diseases. The present study was undertaken to identify novel JIA-predisposing loci using genome-wide approaches.
METHODS: The discovery cohort consisted of Caucasian JIA cases (n = 814) and local controls (n = 658) genotyped on the Affymetrix Genome-Wide SNP 6.0 Array, along with 2,400 out-of-study controls. In a replication study, we genotyped 10 single-nucleotide polymorphisms (SNPs) in 1,744 cases and 7,010 controls from the US and Europe.
RESULTS: Analysis within the discovery cohort provided evidence of associations at 3q13 within C3orf1 and near CD80 (rs4688011) (odds ratio [OR] 1.37, P = 1.88 × 10(-6) ) and at 10q21 near JMJD1C (rs647989 [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 provided further evidence of association for these 4 SNPs (P = 3.6 × 10(-7) for rs4688011, P = 4.33 × 10(-5) for rs6479891, P = 2.71 × 10(-5) for rs12411988, and P = 5.39 × 10(-5) for rs10995450). Gene expression data on 68 JIA cases and 23 local controls showed cis expression quantitative trait locus associations for C3orf1 SNP rs4688011 (P = 0.024 or P = 0.034, depending on the probe set) and JMJD1C SNPs rs6479891 and rs12411988 (P = 0.01 or P = 0.04, depending on the probe set and P = 0.008, respectively). Using a variance component liability model, it was estimated that common SNP variation accounts for approximately one-third of JIA susceptibility.
CONCLUSION: Genetic association results and correlated gene expression findings provide evidence of JIA association at 3q13 and suggest novel genes as plausible candidates in disease pathology.
Copyright © 2012 by the American College of Rheumatology.

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Year:  2012        PMID: 22354554      PMCID: PMC3366043          DOI: 10.1002/art.34429

Source DB:  PubMed          Journal:  Arthritis Rheum        ISSN: 0004-3591


  33 in total

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

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

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10.  CLARITY - ChiLdhood Arthritis Risk factor Identification sTudY.

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