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The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)
  1. Jennifer J Pointon1,
  2. David Harvey1,
  3. Tugce Karaderi1,
  4. Louise H Appleton1,
  5. Claire Farrar1,
  6. Millicent A Stone2,
  7. Roger D Sturrock3,
  8. John D Reveille4,
  9. Michael H Weisman5,
  10. Michael M Ward6,
  11. Matthew A Brown1,7,
  12. B Paul Wordsworth1
  1. 1University of Oxford Institute for Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK
  2. 2Royal National Hospital for Rheumatic Diseases, Bath, UK
  3. 3Centre for Rheumatic Diseases, Division of Immunology, Inflammation and Infection, University of Glasgow, Glasgow, UK
  4. 4University of Texas-Houston Health Science Centre, Houston, Texas, USA
  5. 5Cedars-Sinai Medical Centre, Los Angeles, California, USA
  6. 6Intramural Research Program, NIAMS, Bethesda, Maryland, USA
  7. 7Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Brisbane, Australia
  1. Correspondence to Dr Jennifer Pointon, University of Oxford Institute for Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK; jenny.pointon{at}


Objective To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1.

Methods Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls.

Results The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified.

Conclusions The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

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  • Funding Arthritis Research Campaign, Oxford Radcliffe Hospitals Biomedical Research Centre and National Ankylosing Spondylitis Society.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Anglia and Oxford Multicentre Research Ethics Committee, St John's, Thorpe Road, Peterborough, UK.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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