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SAT0011 Replication of A Distinct Psoriatic Arthritis Risk Variant at IL23R
  1. A. Budu-Aggrey1,2,
  2. J. Bowes1,
  3. S. Lohr3,
  4. S. Uebe3,
  5. M.I. Zervou4,
  6. P. Helliwell5,
  7. A.W. Ryan6,
  8. D. Kane7,
  9. E. Korendowych8,
  10. E. Giardina9,
  11. J. Packham10,
  12. R. McManus6,
  13. O. FitzGerald11,
  14. N. McHugh8,
  15. F. Behrens12,
  16. H. Burkhardt12,
  17. U. Huffmeier3,
  18. P. Ho1,13,
  19. J. Martin14,
  20. S. Castañeda15,
  21. G. Goulielmos4,
  22. A. Reis3,
  23. A. Barton1,2,13
  1. 1Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester
  2. 2NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester, United Kingdom
  3. 3Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
  4. 4Laboratory of Molecular Medicine and Human Genetics, Department of Internal Medicine, University of Crete, Heraklion, Greece
  5. 5NIHR-Leeds Musculoskeletal Biomedical Research Unit Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
  6. 6Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin
  7. 7Adelaide and Meath Hospital and Trinity College Dublin, Dublin, Ireland
  8. 8Royal National Hospital for Rheumatic Diseases and Dept Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
  9. 9Department of Biomedicine and Prevention, University of Rome 'Tor Vergata' and Laboratory of Molecular Genetics UILDM, Fondazione Santa Lucia IRCCS, Rome, Italy
  10. 10Rheumatology department, Haywood Hospital, Health Services Research Unit, Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, United Kingdom
  11. 11Department of Rheumatology, St. Vincent's University Hospital, UCD School of Medicine and Medical Sciences and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
  12. 12Division of Rheumatology and Fraunhofer IME-Project-Group Translational Medicine and Pharmacology, Goethe University, Frankfurt, Germany
  13. 13The Kellgren Centre for Rheumatology, Central Manchester Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom
  14. 14Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18016
  15. 15Department of Rheumatology, Hospital la Princesa, IIS-IPrincesa, Madrid 28006, Spain


Background Psoriatic arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. Although the majority of PsA genetic risk loci identified also confer risk for psoriasis, we have recently reported evidence of loci that are associated with PsA and not psoriasis, including an association at the IL23R locus which is also independent of a psoriasis variant at the same locus.

Methods The PsA-specific SNP rs12044149, and the psoriasis SNP rs9988642 at the IL23R locus were genotyped in a cohort of 914 PsA cases and 6,945 controls from Spain, Crete, Germany and the UK, with the Life Technologies QuantStudio genotyping platform. Association testing was carried out using PLINK, and a meta-analysis was performed with PsA Immunochip data (1,962 cases, 8,923 controls). Genotype data was also available from the psoriasis WTCCC2 study (excluding known PsA, n=1,784) to compare effect sizes between PsA and psoriasis using multinomial logistic regression in Stata, and to directly compare PsA and psoriasis genotypes. Credible SNP sets were calculated for the PsA and psoriasis IL23R associations using the Bayesian refinement method, and functionally annotated.

Results We replicated the association rs12044149 with PsA (P=4.03x10–6), which remained significant when conditioning upon the psoriasis variant, rs9988642 (Pcond=4.86x10–6), and reached genome-wide significance during meta-analysis of the combined PsA dataset (Pmeta=4.76x10–20). Only a modest association was found for rs9988642 (P=0.04), with no genome-wide significance found during meta-analysis (P=4.61x10–4). Within the psoriasis dataset, this association remained significant when conditioning upon rs12044149 (P=1.0x10–07 vs. Pcond=1.63x10–5). Effect estimates for rs12044149 were significantly different between PsA and psoriasis (P=2.0x10–3), and direct comparison of genotypes for PsA and psoriasis found the risk allele to be significantly increased in PsA (P=4.52x10–4, OR=1.3). Credible SNPs for rs12044149 mapped to promoter and enhancer regions within memory CD8+ T cells, which we have previously reported to be critical for PsA.

Conclusions We have successfully replicated a PsA-specific (associated with PsA but not psoriasis) risk variant at the IL23R locus in an independent cohort, confirming rs12044149 to be distinct from rs9988642 (r2=0.02). This gives five PsA-specific associations that have now been identified.

Disclosure of Interest None declared

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