Genome‐wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13
Year: 2012
Type: article
Study design: Observational Study
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.
Source: Arthritis & Rheumatism
DOI: 10.1002/art.34429
Authors: Susan D. Thompson, 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
Institutions: Cincinnati Children's Hospital Medical Center, Wake Forest University, Medical University of South Carolina, University of Manchester, German Center for Pediatric and Adolescent Rheumatology, Emory University, University of Utah, Texas Scottish Rite Hospital for Children, The University of Texas Southwestern Medical Center, Alfred I. duPont Hospital for Children
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Wellcome Trust, Versus Arthritis, National Institutes of Health, Wake Forest School of Medicine, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1221319583, G1260873166, G1611598778, G171560216, G2015297407, WTCCC2 core activities, G256990367, Defining the complex genetics of JIA, HLA/KIR Region Genetics in Pediatric Arthritis, RESEARCH REGISTRY FOR JUVENILE RHEUMATOID ARTHRITIS, G44085036, G495078796, G4956339092, G498736859, G5009335695, G6833652438, Cincinnati Rheumatic Disease Core Center, Identification of Genetic Susceptibility in Adolescent Idiopathic Scoliosis
OpenAlex ID: W2018516739