Decoding diabetes
Twelve new genes associated with type 2 diabetes have been identified in the largest study yet of the connections between differences in people’s DNA and their risk of diabetes.
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. The challenge will be to turn these genetic findings into better ways of treating and preventing the condition.”
Professor Mark McCarthy of the Wellcome Trust Centre for Human Genetics at Oxford University
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 [the cells in the pancreas that produce insulin] that an individual has. 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.”
Professor Mark McCarthy of the Wellcome Trust Centre for Human Genetics at Oxford University
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.
“That we have been able to expand the catalogue of genetic regions known to contribute to type 2 diabetes by nearly a third in a single study serves to highlight the importance of international collaboration to tease out new clues from large samples. But many challenges remain. Each individual variant must be deciphered and its effects understood in the context of the complex tapestry of biological mechanisms underlying type 2 diabetes.”
Dr Eleftheria Zeggini from the Wellcome Trust Sanger Institute and an author on the study
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.
“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.”
Dr Jim Wilson Royal Society University Research Fellow at the University of Edinburgh and a member of the research team
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.”
Professor Mark McCarthy of the Wellcome Trust Centre for Human Genetics at Oxford University
Funding
A full list of funding agencies is available at the Nature Genetics website.
Participating Centres
A full list of participating centres is available at the Nature Genetics website.
More information
Publications:
Selected websites
Diabetes UK
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.
Medical Research Council
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.
Medical Sciences Division - Oxford University
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.
The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.
The Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
