A genome-wide search for type 2 diabetes genes, using 50,000 DNA samples, is now moving from initial discovery to rigorous confirmation. Most diabetes after early adulthood is type 2, affecting nearly 10 percent of the global population. Despite this, the biological processes that trigger the disease remain poorly understood. The researchers have completed the largest genome-wide association study for diabetes to date, but initial signals must be separated from false positives caused by chance or error. This proposal funds that confirmation work, followed by studies of how confirmed genes interact with environmental factors such as poor diet and lack of exercise. If successful, the project will produce a validated set of diabetes-susceptibility genes. This could reveal new biological pathways involved in the disease, pointing toward targets for prevention or treatment. The researchers will also test whether genetic differences can predict an individual’s risk of developing diabetes or indicate which treatments might work best for them. The work is a direct translation of fundamental genetic discovery into clinical and biological insight, with no immediate practical application but clear potential to reshape how diabetes is understood and managed.
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Diabetes is a major and growing cause of disease and death in the UK and beyond. Most diabetes arising after early adulthood is due to ?type 2 diabetes?: almost 10 percent of the world?s population either has this condition or will develop it during their lifetime. Despite this global importance, understanding of the processes which lead to development of type 2 diabetes is far from complete, and much needs to be done to develop more effective approaches to prevention and treatment. One of the most promising routes to a better understanding of diabetes comes from identifying the genes which influence an individual?s predisposition to develop the disease. In recent years, there have been some promising developments and several such genes have been identified. More recently, through advances in knowledge and technology that have followed the sequencing of the human genome, it has become possible to search for such genes in a systematic and ?genomewide? fashion. The applicants on this proposal are currently completing such a ?genomewide association? study (the largest yet conducted into the genetics of diabetes). Analysis of the experimental data will commence shortly and will provide initial clues to the locations of many novel diabetes genes. However, a great deal of work will still be required to separate real effects from spurious findings due to chance or error, and to establish beyond doubt the identities of the genes involved. This work, which involves studying a further 50,000 DNA samples, occupies the first part of our research proposal. With such a set of confirmed diabetes-susceptibility signals in hand, we aim to translate these discoveries into an improved understanding of the biology of diabetes. We will do this in various ways: for instance, by studying how these genes interact with environmental factors (poor diet, lack of exercise) to influence risk of diabetes. Finally, we want to see whether it is practical to use this genetic information to improve the treatment and prevention of diabetes. We will ask whether the genetic differences we have identified will allow us to predict how likely it is that a given individual will develop diabetes and which treatments may be particularly beneficial. The work will be performed by groups in Oxford, Exeter and Dundee who have spent the last decade working together to understand the causes of type 2 diabetes. The funding requested will enable them to make major strides towards this goal.
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