Genetics and genomics
(Lead: Professor Jane Worthington, Deputy: Professor Wendy Thomson)
This division undertakes a major research programme focussing on the identification and characterisation of genetic variants that influence susceptibility to and outcome of arthritic diseases including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, systemic sclerosis and chronic pain. All the diseases investigated are thought to be complex conditions for which susceptibility is determined by a combination of genetic and environmental or lifestyle factors. The benefits of being based in an epidemiological environment are therefore considerable, with the establishment of large well-characterised cohorts of cases, often followed longitudinally, underpinning high quality genetic studies.
Recent technological advances have resulted in significant successes in the identification of genetic risk factors for complex diseases and the Arthritis Research UK Epidemiology Unit has been at the forefront of these studies for rheumatoid arthritis (RA) and juvenile idiopathic arthritis. Our involvement in the Wellcome Trust Case Control Consortium resulted in the first whole genome association study of rheumatoid arthritis and our subsequent studies have resulted in the identification of novel RA disease susceptibility loci. Future work will focus on detailed characterisation of these loci and the investigation of the interactions between the loci and other disease risk factors in order to advance our understanding of the variable patterns of presentation and progression of this disease.
Genetic factors are also thought to influence response to treatments and we have projects focussing on the three major therapies:
- Methotrexate (Wendy Thomson)
- Anti-TNF biologics (Anne Barton)
- Steroids (Ian Bruce in collaboration with Rachelle Donn)
Children too can be affected by inflammatory arthritis (juvenile idiopathic arthritis or JIA) and through the work of Wendy Thomson and her team, the Unit is recognised as an international leader in this field. The Unit houses one of the world’s largest cross sectional collections and the only prospective study of JIA (CAPS).
We also investigate some of the rarer inflammatory arthropathies including systemic sclerosis (Ariane Herrick) and psoriatic arthritis (Anne Barton). Collaboration with dermatology colleagues in Manchester (Professor Chris Griffiths) has allowed us to establish a unique study comparing psoriasis, psoriatic arthritis and inflammatory arthritis.
To date, much of research has been aimed at identifying genetic risk factors and although considerable progress has been made we now face the challenge of investigating the identified loci in detail. Our involvement in the international consortium study Immunochip, is key in our fine mapping studies for a large number of RA susceptibility loci that are also associated with other autoimmune diseases. Ultimately we aim to determine how subtle changes in the genetic code result in altered function or level of production of proteins and how in turn this influences the disease process. To achieve this we are establishing collaborations with many national and international researchers including a number within The University of Manchester.
Collaborations
National and international collaborations are key to our work as exemplified by our contribution to the EU Autocure Programme and established collaborations with all the major international groups researching in this area including:
- Peter Gregersen, The Feinstein Institute for Medical Research, USA
- Robert Plenge and Souyma Raychaudhuri, Broad Institute of Harvard and Massachusetts Institute of Technology, USA
- Lars Klareskog, Karolinska Insitute, Sweden
- Ele Zeggini, Wellcome Trust Sanger Institute, Cambridge, UK
- John Todd, Cambridge Institute for Medical Research, UK
- Iain McInnes, Glasgow Biomedical Research Centre, UK
- UKRAG consortium members
- Andy Cope, Kings College, London, UK
- Sue Thompson, Cincinnati Children's Hospital Medical Center, USA
- Lucy Wedderburn, Institute of Child Health, London, UK
- Pat Woo, The Windeyer Institute, London, UK
- Katherine Siminovitch, Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Canada
- André Reis, Institute of Human Genetics University of Erlangen-Nürnberg, Germany
