07 Jun 07

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, today publishes 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 is chaired by Professor Peter Donnelly of Oxford University and involves other Oxford researchers in leading roles.

The study 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.

'Many of the most common diseases are very complex, part nature and nurture, with genes interacting with our environment and lifestyles,' says Professor Donnelly. 'By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs and which people are most at risk and, in time, to produce more effective, more personalised treatments.'

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.

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.

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, and led by Professor Mark McCarthy from the University of Oxford and Professor Andrew Hattersley of the Peninsula Medical School, Exeter. It has found independently a major gene region on chromosome 9 identified by independent studies on coronary heart disease.

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), led by Professor John Todd from the University of Cambridge. For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.

'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.'

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.

'Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works,' says Professor Donnelly. 'We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedlyherald major advances in how we understand and tackle disease in the future.'