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. 2013 Jun;45(6):664-9.
doi: 10.1038/ng.2614. Epub 2013 Apr 21.

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

Anne Hinks  1 , Joanna Cobb, Miranda C Marion, Sampath Prahalad, Marc Sudman, John Bowes, Paul Martin, Mary E Comeau, Satria Sajuthi, Robert Andrews, Milton Brown, Wei-Min Chen, Patrick Concannon, Panos Deloukas, Sarah Edkins, Stephen Eyre, Patrick M Gaffney, Stephen L Guthery, Joel M Guthridge, Sarah E Hunt, Judith A James, Mehdi Keddache, Kathy L Moser, Peter A Nigrovic, Suna Onengut-Gumuscu, Mitchell L Onslow, Carlos D Rosé, Stephen S Rich, Kathryn J A Steel, Edward K Wakeland, Carol A Wallace, Lucy R Wedderburn, Patricia Woo; Boston Children's JIA Registry; British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group; Childhood Arthritis Prospective Study (CAPS); Childhood Arthritis Response to Medication Study (CHARMS); German Society for Pediatric Rheumatology (GKJR); JIA Gene Expression Study; NIAMS JIA Genetic Registry; TREAT Study; United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium (UKJIAGC); John F Bohnsack, Johannes Peter Haas, David N Glass, Carl D Langefeld, Wendy Thomson, Susan D Thompson
Affiliations

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

Anne Hinks et al. Nat Genet. 2013 Jun.

Abstract

We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.

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Figures

Figure 1
Figure 1. Manhattan plot of association statistics for oligoarticular and RF negative polyarticular juvenile idiopathic arthritis risk loci
The upper dashed black line indicates the threshold for genome wide significance (p < 5 × 10-8, loci reaching this threshold are highlighted in bold font and individual SNPs mapping to these loci are shown in red. The lower dashed grey line indicates the threshold for suggestive association (p < 1 × 10-6 and p > 5 × 10-8), loci reaching this threshold are labeled in non-bold font.
Figure 2
Figure 2. Association results for the HLA region (chromosome 6, 25-34 Mb)
SNPs are color-coded by odds ratio (OR) strata.
See this image and copyright information in PMC

Comment in

References

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