Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease

Stephen Eyre, Anne Hinks, John Bowes, Edward Flynn, Paul Martin, Anthony G. Wilson, Ann W. Morgan, Paul Emery, Sophia Steer, Lynne J Hocking, David M. Reid, Pille Harrison, Paul Wordsworth, Wendy Thomson, Jane Worthington, Anne Barton, BIRAC consortium

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Abstract

Introduction: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD).

Methods: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant.

Results: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 x 10(-4)). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold.

Conclusions: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

Original languageEnglish
Article numberR175
Number of pages6
JournalArthritis Research & Therapy
Volume12
Issue number5
DOIs
Publication statusPublished - 20 Sep 2010

Keywords

  • juvenile idiopathic arthritis
  • genome-wide association
  • risk
  • loci
  • classification
  • expression
  • common

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