Skip to main content

Advertisement

SpringerLink
Log in

What Have Genome-Wide Studies Told Us About Psoriatic Arthritis?

  • PSORIATIC ARTHRITIS (O FITZGERALD AND P HELLIWELL, SECTION EDITORS)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

There is convincing evidence to suggest a strong genetic component to psoriatic arthritis (PsA), with studies reporting a 40-fold risk to first-degree relatives of patients with disease. However, compared with rheumatoid arthritis, our understanding of the genetic etiology of PsA is less well-developed. Only three modestly sized genome-wide association studies of PsA have been undertaken to date, but they have identified the HLA-C region, IL12B, TRAF3IP2, and FBXL19 genes as being associated with PsA susceptibility. Results of genome-wide association studies of psoriasis and rheumatoid arthritis have been used to identify candidate genes for subsequent testing in PsA and have led to the identification of additional susceptibility factors for PsA. Most show overlap with psoriasis, whereas the overlap with rheumatoid arthritis is less pronounced. However, two loci show strong evidence for association with PsA but not psoriasis: HLA-B27 and the IL-13 gene locus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gladman DD, Farewell VT, Pellett F, et al. HLA is a candidate region for psoriatic arthritis. evidence for excessive HLA sharing in sibling pairs. Hum Immunol. 2003;64:887–9.

    Article  PubMed  CAS  Google Scholar 

  2. Myers A, Kay LJ, Lynch SA, Walker DJ. Recurrence risk for psoriasis and psoriatic arthritis within sibships. Rheumatology (Oxford). 2005;44:773–6.

    Article  CAS  Google Scholar 

  3. Chandran V, Schentag CT, Brockbank JE, et al. Familial aggregation of psoriatic arthritis. Ann Rheum Dis. 2009;68:664–7.

    Article  PubMed  CAS  Google Scholar 

  4. • Karason A, Love TJ, Gudbjornsson B: A strong heritability of psoriatic arthritis over four generations--the Reykjavik Psoriatic Arthritis Study. Rheumatology (Oxford) 2009, 48(11):1424–8. This provides convincing evidence for a genetic contribution to PsA and allows comparison of the genetic effect with RA.

    Article  Google Scholar 

  5. Liu Y, Helms C, Liao W, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease Loci. PLoS Genet. 2008;4:e1000041.

    Article  PubMed  Google Scholar 

  6. •• Huffmeier U, Uebe S, Ekici AB, et al.: Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 2010, 42:996–999. This was the first well-powered GWAS of PsA; it identified a susceptibility gene, TRAF3IP2, and provided functional evidence about how the genetic variation may affect cell function.

    Article  PubMed  Google Scholar 

  7. Cargill M, Schrodi SJ, Chang M, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet. 2007;80:273–90.

    Article  PubMed  CAS  Google Scholar 

  8. Stuart PE, Nair RP, Ellinghaus E, et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet. 2010;42:1000–4.

    Article  PubMed  CAS  Google Scholar 

  9. • Chandran V: The genetics of psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol 2012, Jan 25. [Epub ahead of print]. This is a comprehensive summary of results of psoriasis GWAS to date.

  10. Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010;42:508–14.

    Article  PubMed  CAS  Google Scholar 

  11. Bowes J, Ho P, Flynn E, et al.: Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort. Ann Rheum Dis 2012, Feb 10. [Epub ahead of print].

  12. Ellinghaus E, Stuart PE, Ellinghaus D, et al.: Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. J Invest Dermatol 2011, Dec 15. doi:10.1038/jid.2011.415. [Epub ahead of print].

  13. Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41:199–204.

    Article  PubMed  CAS  Google Scholar 

  14. Thomson W, Barton A, Ke X, et al. Rheumatoid arthritis association at 6q23. Nat Genet. 2007;39:1431–3.

    Article  PubMed  CAS  Google Scholar 

  15. Musone SL, Taylor KE, Lu TT, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008;40:1062–4.

    Article  PubMed  CAS  Google Scholar 

  16. Franke A, McGovern DP, Barrett JC, et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet. 2010;42:1118–25.

    Article  PubMed  CAS  Google Scholar 

  17. Winchester R, Minevich G, Steshenko V, et al.: HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype. Arthritis Rheum 2011, Oct 17. doi:10.1002/art.33415. [Epub ahead of print].

  18. Eder L, Chandran V, Pellet F, et al. Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. Ann Rheum Dis. 2012;71:50–5.

    Article  PubMed  Google Scholar 

  19. Ho PY, Barton A, Worthington J, et al. HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis. Ann Rheum Dis. 2007;66:807–11.

    Article  PubMed  CAS  Google Scholar 

  20. Ellinghaus E, Ellinghaus D, Stuart PE, et al. Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet. 2010;42:991–5.

    Article  PubMed  CAS  Google Scholar 

  21. Strange A, Capon F, Spencer CC, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42:985–90.

    Article  PubMed  CAS  Google Scholar 

  22. •• Duffin KC, Freeny IC, Schrodi SJ, et al.: Association between IL13 polymorphisms and psoriatic arthritis is modified by smoking. J Invest Dermatol 2009, 129:2777–83. This was the first study to show that stratification analysis of psoriasis GWAS might lead to identification of PsA-specific loci.

    Article  PubMed  CAS  Google Scholar 

  23. Bowes J, Eyre S, Flynn E, et al. Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris. Ann Rheum Dis. 2011;70:1016–9.

    Article  PubMed  Google Scholar 

  24. Eder L, Chandran V, Pellett F, et al. IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients. Ann Rheum Dis. 2011;70:1594–8.

    Article  PubMed  CAS  Google Scholar 

  25. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–8.

    Article  PubMed  CAS  Google Scholar 

  26. Bowes J, Orozco G, Flynn E, et al. Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis. Ann Rheum Dis. 2011;70:1641–4.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the NIHR Manchester Biomedical Research Centre for support. Dr. Barton is funded by Arthritis Research UK.

Disclosure

AB has provided consultancy services to Eli-Lilly Pharmaceutical Company but not in relation to any of the work presented here.

Dr. Bluett reported no potential conflicts of interest relevant to this article.

Author information

Authors and Affiliations

  1. Arthritis Research UK Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester, England, M13 9PT, UK

    James Bluett

  2. Arthritis Research UK Epidemiology Unit, University of Manchester, Arthritis Research UK Epidemiology Unit and Kellgren Centre for Rheumatology, Manchester Academy of Health Sciences, University of Manchester and Manchester Royal Infirmary, Oxford Road, Manchester, England, M13 9PT, UK

    Anne Barton

Authors
  1. James Bluett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Barton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Barton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bluett, J., Barton, A. What Have Genome-Wide Studies Told Us About Psoriatic Arthritis?. Curr Rheumatol Rep 14, 364–368 (2012). https://doi.org/10.1007/s11926-012-0255-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-012-0255-5

Keywords

Search

Navigation