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Largest Ever Study of Genetics Behind Common Diseases Published

The largest ever study of the genetics behind common diseaseslike diabetes, rheumatoid arthritis, and coronary heart diseasehas been published in the journals Nature and Nature Genetics.

The nine-million-pound Wellcome Trust Case Control Consortium is one of the UKs largest and most successful academic collaborations to date, which brought together 50 leading research groups and 200 scientists in the field of human genetics from dozens of institutions in the country.

Over two years, they examined DNA samples from 17,000 people across the UK, and 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 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 personalized treatments," he adds.

The study has substantially increased the number of genes known to play a role in the development of some of the most common diseases. Many genes were found in areas of the genome that were 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. 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," says Dr Mark Walport, Director of the Wellcome Trust, the UK's largest medical research charity, which funded the study.

"This research shows that it is possible to analyze 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, behavioral and environmental factors that conspire to cause disease," he added.

During the study, the researchers found 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, a gene called PTPN2 has been found which links the two autoimmune diseases.

The study also confirmed the importance of a process known as autophagy or self eating in the development of Crohn's disease. Autophagy is responsible for clearing unwanted material, such as bacteria, from within cells.

"The link between type 1 diabetes and Crohn's disease is one of the most exciting findings to come out of the Consortium," says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes.

"It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn's disease are increasingly well understood and we hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future," he adds.

The researchers analysed DNA samples taken from 2,000 patients and 3,000 control subjects to identify common genetic variations for seven major diseasesbipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis, and type 1 and type 2 diabetes. They are planning to 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 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 undoubtedly herald major advances in how we understand and tackle disease in the future," he adds.

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 of which are expected later this year.


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