Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome-wide association analysis

Anne Hinks, Anne Barton, Neil Shephard, Steve Eyre, John Bowes, Michele Cargill, Eric Wang, Xiayi Ke, M. Abinum, M. Becker, A. Bell, A. Craft, E. Crawley, J. David, H. Foster, J. Gardener-Medwin, J. Griffin, A. Hall, M. Hall, A. HerrickP. Hollingworth, L. Holt, S. Jones, G. Pountain, C. Ryder, T. Southwood, I. Stewart, H. Venning, L. Wedderburn, P. Woo, S. Wyatt, Giulia C. Kennedy, Sally John, Jane Worthington, Wendy Thomson

    Research output: Contribution to journalArticlepeer-review


    Objective. Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well-established genetic factors known to contribute to JIA susceptibility, HLA and PTPN22, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA. Methods. A genome-wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single-nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort (n = 2,024). In one region in which association was confirmed, fine-mapping was performed (654 cases and 1,847 controls). Results. Of the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the HLA region, while the second strongest association was with a SNP within the VTCN1 gene. Fine-mapping of that gene was performed, and 10 SNPs were found to be associated with JIA. Conclusion. This study is the first to successfully apply a SNP-based genome-wide association approach to the investigation of JIA. The replicated association with markers in the VTCN1 gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood. © 2009, American College of Rheumatology.
    Original languageEnglish
    Pages (from-to)258-263
    Number of pages5
    JournalArthritis Care & Research
    Issue number1
    Publication statusPublished - Jan 2009


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