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E-GEOD-26554 - Genome-wide association study of juvenile idiopathic arthritis identifies novel susceptibility loci at JMJD1C-NRBF2, IL15 and C3orf1

Status
Released on 23 March 2012, last updated on 1 April 2012
Organism
Homo sapiens
Samples (91)
Array (1)
Protocols (10)
Description
Juvenile idiopathic arthritis (JIA) is the most common chronic childhood rheumatic disease in the Western world. To identify novel JIA predisposing loci, a genome-wide association study (GWAS) in 814 Caucasian JIA cases and 3058 Caucasian controls was completed. After adjusting for the most significant HLA associations, the strongest novel associations included rs6479891 (10q21, odds ratio (OR)=1.59, P=1.3x10-8) and rs10761747 (OR=1.34, P=4.0x10-5) within JMJD1C; rs12719740 (15q26, OR=1.47, P=3.3x10-7) near FAM169B; rs4688011 (3q13, OR=1.33, P=1.1x10-4) within C3orf1 and rs4254850 (4q31, OR=0.85, P=7.8x10-3) near IL15. Eleven SNPs were genotyped in Caucasian replication cohorts (1744 cases, 7010 controls) and meta-analysis continued to provide evidence for association with three of the SNPs (rs6479891, P=4.3x10-5; rs12719740, P=5.2x10-4; rs4688011, P=3.6x10-7). Analysis of expression data from 68 JIA cases and 23 controls overlapping in the GWAS cohort1 and published lymphoblastoid cell lines (LCL)2 showed cis eQTL associations for JMJD1C SNPs (P=0.01 and P=1.6x10-6, respectively), and the C3orf1 SNP (P=5.7x10-6). Peripheral blood samples were obtained from 23 healthy children and 68 children with JIA. RNA was purified from Ficoll-isolated mononuclear cells, fluorescently labeled and then hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were imported using Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization. eQTL analysis were performed using genomewide association data.
Experiment type
transcription profiling by array 
Contacts
Michael Barnes <michael.barnes@cchmc.org>, Anne Hinks, Carl D.Langefeld, Carol Wise, Carols Rosé, David N Glass, J P Hass, John Bohnsack, Marc Sudman, Marilynn Punaro, Mehdi Keddache, Michael G.Barnes, Michael Spigarelli, Michael Wagner, Mimi Ryan, Miranda C Marion, Monica Tsoras, Paula S Ramos, Sampath Prahalad, Susan D Thompson, Timothy D Howard, Wendy Thompson
MIAME
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