Abstract for presentation at 11th International Congress of Human Genetics

A whole genome by association of chronic inflammatory arthritis

  • Dr Giulia Kennedy, Affymetrix, Santa Clara, United States
  • Mr Neil Shephard, University of Manchester, United Kingdom
  • Dr Yaron Turpaz, Affymetrix , Santa Clara, United States
  • Dr Chun Zhang, Affymetrix , Santa Clara, United States
  • Dr Anne Hinks, University of Manchester, United Kingdom
  • Dr Wendy Thomson, University of Manchester, United Kingdom
  • Dr Jane Worthington, University of Manchester, United Kingdom
  • Dr Sally John, University of Manchester, United Kingdom

    • Background: Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are both chronic inflammatory conditions with an autoimmune pathology. In common with other autoimmune diseases, both RA and JIA are heritable and are associated with genes in the MHC. The recent association of the PTPN22 R620W SNP with several autoimmune diseases confirms the hypothesis that there is an underlying common genetic basis in autoimmunity.
    Aim: To identify novel autoimmunity susceptibility loci.
    Methods: 184 healthy adult controls and 449 cases with a chronic autoimmune arthritis and an age at onset <40 years were available for study. Of the cases 168 had a clinical diagnosis of RA and 281 a diagnosis of JIA. 184 healthy adult controls were also available. Genotyping was performed for 115,075 SNPs using the Affymetrix mapping 100K array. The Armitage test for trend was employed to test for association with disease and the false discovery rate (FDR)q-value method was applied to account for the multiple comparisons performed.
    Results: 7,789 SNPs (7%) failed to genotype in >80% of DNAs or failed HWE (p<0.0001) and were excluded. Due to the low power of the study to detect rare disease associated alleles, SNPs with a MAF <5% were not analysed. 82,500 SNPs were therefore analysed for association with arthritis. SNPs were identified for follow up in a second replication cohort. Applying a FDR of 1%, the q-value method generated 32 SNPs that remained significantly associated after correction for multiple testing. In addition, SNPs associated at a less stringent significance threshold (p <0.0001) in regions of linkage in RA and/or JIA were also selected. These included a SNP in LD with the PTPN22 R620W SNP; ODDS 2.07, 95%CI [1.4-3.1], p = 0.00009.
    Discussion: These results suggest that SNPs associated with autoimmune arthritis can be identified using a WGA approach. Replication of associations in a larger cohort will be required to confirm these preliminary results.

    Conference Organiser - ICMS Pty Ltd