The international consortium of scientists, led by Professor Mark McCarthy of the University of Oxford, report their findings in the journal Nature Genetics – 10 years after the first draft of the human genome was announced on 26 June 2000.‘
The signals we have identified provide important clues to the biological basis of type 2 diabetes,’ says Professor McCarthy of the Wellcome Trust Centre for Human Genetics at Oxford University. ‘The challenge will be to turn these genetic findings into better ways of treating and preventing the condition.’
The identification of 12 new genes brings the total number of genetic regions known to be associated with type 2 diabetes to 38. The genes tend to be involved in the working of pancreatic cells that produce the hormone insulin (insulin is crucial for controlling levels of glucose in the blood), the control of insulin’s action in the body, and in cell-cycle regulation.
The findings not only improve understanding of the processes underpinning type 2 diabetes, but give new biological pathways that can be explored as targets for new therapies.
‘One important theme is that several of the genes seem to be important in controlling the number of pancreatic beta-cells that an individual has,’ says Professor McCarthy. (Beta-cells are the cells in the pancreas that produce insulin.) ‘This helps settle a long-standing controversy about the role of beta-cell numbers in type 2 diabetes risk, and points to the importance of developing therapies that are able to preserve or restore depleted numbers of beta-cells.’
The consortium of researchers – from across the UK, Europe, USA and Canada – compared the DNA of over 8,000 people with type 2 diabetes with almost 40,000 people without the condition at almost 2.5 million locations across the genome. They then checked the genetic variations they found in another group including over 34,000 people with diabetes and almost 60,000 controls.
Although the study found 12 new genetic regions where the presence of a particular variation in DNA sequence leads to an increased susceptibility to type 2 diabetes, the individual effects are small. That is, possessing one of these gene variants leads to only a marginal (but clear) increase in the risk of developing the condition. Even in combination, their capacity to predict future risk of diabetes is modest. However, the potential impact of the findings in terms of new biology and possible therapeutic developments could be significant.
Dr Jim Wilson, Royal Society University Research Fellow at the University of Edinburgh and a member of the research team, said: ‘One very interesting finding is that the diabetes susceptibility genes also contain variants that increase the risk of unrelated diseases, including skin and prostate cancer, coronary heart disease and high cholesterol. This implies that different regulation of these genes can lead to many different diseases.’
The researchers are now planning to use the availability of new tools for sequencing the whole human genome to explore further sources of DNA sequence variation that have been missed in previous efforts, in an effort to pin down the remaining genetic basis for type 2 diabetes.
Type 2 diabetes represents one of the most significant global challenges to health. The rapidly rising prevalence of this condition across the world is thought to reflect the impact of widespread changes in lifestyle and diet on genetically susceptible individuals. Currently-available therapies can mitigate the effects of diabetes, but improved approaches for prevention and treatment are urgently required.
‘Gradually we are piecing together clues about why some people get diabetes and others don’t, with the potential for developing better treatments and preventing onset of diabetes in the future,’ says Professor McCarthy.
For more information please contact: Professor Mark McCarthy on 07825 344066 or [email protected] Mark McCarthy is currently in the US, so please bear in mind the time difference.Or the University of Oxford press office on 01865 280530 or [email protected]
Notes to Editors
- The paper ‘Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis’ by Benjamin Voight and colleagues is to be published in Nature Genetics with an embargo of 18.00 UK time on Sunday 27 June 2010.
- The Oxford part of the study was funded by Diabetes UK, the Medical Research Council, the Wellcome Trust and the European Union. A full list of funders for the international consortium is given in the paper.
- Diabetes UK is the leading charity for the three million people in the UK with diabetes. We will spend £6 million on research in 2010 as well as campaign and provide information and support. For more information visit www.diabetes.org.uk
- For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
- The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
- Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.