Evidence for new genes behind rheumatoid arthritis
A major study collaborative study published on Wednesday, June 6 has implicated several genes that play a part in the disease process of rheumatoid arthritis for the first time.
The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease, published its results in the journals Nature and Nature Genetics.
The £9 million study is one of the UK's largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics from dozens of UK institutions. Over two years, they have analysed almost 10 billion pieces of genetic information.
The Wellcome Trust Case Control Consortium is supported by the Medical Research Council, British Heart Foundation, Juvenile Diabetes Research Foundation, Diabetes UK, the Arthritis Research Campaign (arc), the National Association for Colitis & Crohn's Disease and MDF The Bipolar Organisation.
A number of markers were found to be associated with rheumatoid arthritis, implicating several genes for the first time in this disease process. Further work will be required to validate the findings and understand how the variation within key genes influences the development of RA, the course of the disease and response to treatment.
Professor Jane Worthington from the Arthritis Research Campaign epidemiology unit at the University of Manchester, said: "Rheumatoid arthritis is a complex disease with considerable variation observed between patients both in terms of the severity of the symptoms and the response to therapies. The findings of the WTCCC make a major step forward in terms of understanding how multiple genetic factors may influence this disease process.
"Patients with rheumatoid arthritis are also at increased risk of other conditions such as cardiovascular disease and an increase in type 1 diabetes has been observed in families with rheumatoid arthritis. The collaborative nature of this ground breaking study will greatly facilitate our investigation of genetic risk factors that may be common to different diseases.
"Despite recent advances in the treatment of rheumatoid arthritis this disease continues to present a significant healthcare burden. Greater understanding of the genetic basis of susceptibility is important to the development of novel therapeutic approaches particularly those aimed at arresting the disease process before significant disability has occurred."
Professor Alan Silman, medical director of the Arthritis Research Campaign: "Rheumatoid arthritis is a serious form of arthritis affecting around 387,000 people and we have known for some time that there is a major genetic component to this disease. The results from this unique study have highlighted some exciting opportunities to explore the role of genes, previously unsuspected as being important in increasing the risk of arthritis. We will be supporting urgent follow-up of these findings which hopefully could lead to both an increased understanding of what cause rheumatoid arthritis as well as pointing to possible new cures."
"Many of the most common diseases are very complex, part 'nature' and 'nurture', with genes interacting with our environment and lifestyles," says Professor Peter Donnelly, Chair of the Consortium, who is based at the University of Oxford. "By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments."
The study has substantially increased the number of genes known to play a role in the development of some of our most common diseases. Many of these genes that have been found are in areas of the genome not previously thought to have been related to the diseases.
"Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people," says Dr Mark Walport, Director of the Wellcome Trust, the UK's largest medical research charity, which funded the study. "What has been achieved in this research is the analysis of half a million genetic variants in each of seventeen thousand individuals, with the discovery of more than ten genes that predispose to common diseases.
"This research shows that it is possible to analyse human variation in health and disease on an enormous scale. It shows the importance of studies such as the UK Biobank, which is seeking half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation. New preventive strategies and new treatments depend on a detailed understanding of the genetic, behavioural and environmental factors that conspire to cause disease."
Researchers analysed DNA samples taken from people in the UK – 2,000 patients for each disease and 3,000 control samples – to identify common genetic variations for seven major diseases. These are bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes. For each disease, the researchers will study larger population samples to confirm their results.
"Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that our approach of analysing just a subset of the variation works," says Professor Donnelly. "This approach will undoubtedly herald major advances in how we understand and tackle disease in the future."
Further analysis as part of the Consortium will be looking at tuberculosis (TB), breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis. The results are expected later this year.
