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.
"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."
Over two years, the consortium analyzed almost 10 billion pieces of genetic information. It has substantially increased the number of genes known to play a role in the development of some of our most common diseases.
Amongst the most significant new findings are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn's disease (a type of inflammatory bowel disease). For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.
Research from the Consortium has already played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes, published in April in advance of the main study. It has found independently a major gene region on chromosome 9 identified by independent studies on coronary heart disease.
Researchers analyzed 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.
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.
Rheumatoid Arthritis Key Findings
A number of markers were found to be associated with RA, 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, University of Manchester says, "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."
Alan Silman, medical director of the Arthritis Research Campaign says, "Rheumatoid arthritis is a serious form of arthritis and we have known for some time that there is an 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."