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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hinks, A; Barton, A; Shephard, N; Eyre, S; Bowes, J; Cargill, M; Wang, E; Ke, X; Kennedy, GC; John, S; Worthington, J; Thomson, W; British Society of Paediatric and Adolescent Rheumatology Study Group,

Published Date

  • January 2009

Published In

Volume / Issue

  • 60 / 1

Start / End Page

  • 258 - 263

PubMed ID

  • 19116933

Pubmed Central ID

  • PMC3001111

International Standard Serial Number (ISSN)

  • 0004-3591

Digital Object Identifier (DOI)

  • 10.1002/art.24179


  • eng

Conference Location

  • United States