Genetic Predisposition to Psoriatic Arthritis Localized To Chromosome 5

psoriasis_knees Interview with:
Professor Anne Barton FRCP PhD and
Dr John Bowes PhD

Centre for Musculoskeletal Research and
Centre for Genetics and Genomics,
The University of Manchester, Manchester UK

Medical Research: What is the background for this study?

Response: Psoriatic arthritis (PsA) is an inflammatory condition causing pain and stiffness in joints and tendons. Approximately one third of patients with psoriasis will go on to develop PsA resulting in a reduction in their quality of life caused by increasing disability and additional health complications. A key area of research within the Arthritis Research UK Centre for Genetics and Genomics in the Centre for Musculoskeletal Research is the identification of risk factors for the development of Psoriatic arthritis; this will allow us to understand the underlying cause of disease and ultimately help identify psoriasis patients at high risk of PsA, allowing early treatment to be introduced to reduce the impact of PsA.

Our study focuses on the identification of genetic risk factors for Psoriatic arthritis; we compared the frequency of genetic variants, referred to as single nucleotide polymorphisms (SNPs), between large numbers of DNA samples from patients with PsA and healthy control samples. When the frequency of the SNP is significantly different between cases and controls, the SNP is said to be associated with risk of developing Psoriatic arthritis and this association is interpreted as being important in the disease process.

Medical Research: What are the main findings?

Response: When we analysed the data from the study we found a new association to SNPs on chromosome 5, and when we investigated these SNPs for association with skin-only psoriasis, we did not find any evidence for association. In addition, we also found SNPs that were specifically associated with Psoriatic arthritis at a gene on chromosome 1. This gene is known to be associated with psoriasis, but our results show that there are different SNPs associated with PsA and psoriasis at this gene. Hence, our results identify new SNPs that are specifically associated with PsA.

In addition, identifying which cells are the key drivers of inflammation in Psoriatic arthritis will help us to focus on how the genetic changes act in those cells to cause disease. Our results show that many of the PsA associated SNPs occur in regions of the genome that are important in the function of CD8+ cells, an important cell type in the immune system.

Medical Research: What should clinicians and patients take away from your report?

Response: By identifying genes that predispose to Psoriatic arthritis but not psoriasis, we hope in the future to be able to test patients with psoriasis to find those at high risk of developing Psoriatic arthritis. Excitingly, it raises the possibility of introducing treatments to prevent the development of PsA in those individuals in the future.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Our study has begun to reveal key insights into the genetics of PsA that explain fundamental differences between psoriasis and Psoriatic arthritis. The results demonstrate that future studies attempting to identify genes specifically associated with PsA would benefit from directly comparing findings from patients with PsA and patients with psoriasis alone approach. Our findings also highlight that CD8+ cells are likely to be the key drivers of inflammation in PsA and identify this as the key cell type to focus on in future studies investigating the biological impact of these SNPs.


John Bowes, Ashley Budu-Aggrey, Ulrike Huffmeier, Steffen Uebe, Kathryn Steel, Harry L. Hebert, Chris Wallace, Jonathan Massey, Ian N. Bruce, James Bluett, Marie Feletar, Ann W. Morgan, Helena Marzo-Ortega, Gary Donohoe, Derek W. Morris, Philip Helliwell, Anthony W. Ryan, David Kane, Richard B. Warren, Eleanor Korendowych, Gerd-Marie Alenius, Emiliano Giardina, Jonathan Packham, Ross McManus, Oliver FitzGerald, Neil McHugh, Matthew A. Brown, Pauline Ho, Frank Behrens, Harald Burkhardt, Andre Reis, Anne Barton. Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nature Communications, 2015; 6: 6046 DOI: 10.1038/ncomms7046 Interview with:, & Professor Anne Barton FRCP PhD Centre Lead and Dr John Bowes PhD (2015). Genetic Predisposition to Psoriatic Arthritis Localized To Chromosome 5