6th June 2007

Largest ever study of genetics of common diseases

Wellcome Trust Case Control Consortium and genetics of seven common diseases

Genome-wide scan

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 (publication 1 & 2).

The £9 million study is one of the UK's largest and most successful academic collaborations to date. It 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.

The study capitalises on the knowledge built by the Human Genome and HapMap Projects, two consortia in which the Wellcome Trust Sanger Institute played a leading role.

Dr Panos Deloukas, who led the team at the Sanger Institute, explains: "The index of variation built from the HapMap has dramatically accelerated our ability to search for genes involved in human disease. Aided by highly parallel technologies we have put this knowledge to practise, testing 500,000 variants in the human genome for association to seven major common diseases."

Although the human genome is made up of more than three billion sub-units of DNA, called nucleotides (or bases), most of these show little in the way of differences between individuals. A substantial part of the variation in DNA sequence between individuals is due to single-nucleotide polymorphisms (differences), also known as SNPs. There are approximately 8 million common SNPs in European populations. Most of them can be interrogated by a subset because SNPs that lie close together on chromosomes often are genetically linked.

" By making the consortium data available to the research community we are maximising the use of this resource, an approach that will empower further studies "

Dr Panos Deloukas

Research from the Consortium had 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. It has found independently a major gene region on chromosome 9 identified by independent studies on coronary heart disease.

"This is UK genetics and genomics at its best," said Professor Allan Bradley, Director of the Wellcome Trust Sanger Institute. "The application of genome scale analysis to thousands of samples across several diseases has never been attempted on this scale before. The fact that so many investigators recognized that the best way forward was to come together, pool their resources and work as part of a large consortium with specialised centres for patient collection, data generation and analysis for the greater good has been a spectacular success."

"As a result we now have new leads which will provide insight into these common diseases. This will ultimately translate into better treatments."

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.

"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."

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). For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.

"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 personalised treatments."

The study has also confirmed the importance of a process known as autophagy in the development of Crohn's disease. Autophagy, or "self eating", is responsible for clearing unwanted material, such as bacteria, from within cells. The may be key to the interaction of gut bacteria in health and in inflammatory bowel disease and could have clinical significance in the future.

"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."

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 bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes. For each disease, the researchers will study larger population samples to confirm their results.

"By making the consortium data available to the research community we are maximising the use of this resource, an approach that will empower further studies" added Dr Deloukas.

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.

Notes to Editors

Publication details

  • Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.

    Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, Bailey R, Nejentsev S, Field SF, Payne F, Lowe CE, Szeszko JS, Hafler JP, Zeitels L, Yang JH, Vella A, Nutland S, Stevens HE, Schuilenburg H, Coleman G, Maisuria M, Meadows W, Smink LJ, Healy B, Burren OS, Lam AA, Ovington NR, Allen J, Adlem E, Leung HT, Wallace C, Howson JM, Guja C, Ionescu-Tîrgovişte C, Genetics of Type 1 Diabetes in Finland, Simmonds MJ, Heward JM, Gough SC, Wellcome Trust Case Control Consortium, Dunger DB, Wicker LS and Clayton DG

    Nature genetics 2007;39;7;857-64

  • Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility.

    Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, Roberts RG, Nimmo ER, Cummings FR, Soars D, Drummond H, Lees CW, Khawaja SA, Bagnall R, Burke DA, Todhunter CE, Ahmad T, Onnie CM, McArdle W, Strachan D, Bethel G, Bryan C, Lewis CM, Deloukas P, Forbes A, Sanderson J, Jewell DP, Satsangi J, Mansfield JC, Wellcome Trust Case Control Consortium, Cardon L and Mathew CG

    Nature genetics 2007;39;7;830-2

  • Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

    Wellcome Trust Case Control Consortium

    Nature 2007;447;7145;661-78


The principal funder of this project was the Wellcome Trust.

Case collections were funded by: Arthritis Research Campaign, BDA Research, British Heart Foundation, British Hypertension Society, Diabetes UK, Glaxo-Smith Kline Research and Development, Juvenile Diabetes Research Foundation, National Association for Colitis and Crohn's disease, SHERT (The Scottish Hospitals Endowment Research Trust), St Bartholomew's and The Royal London Charitable Foundation, UK Medical Research Council, UK NHS R&D and the Wellcome Trust. Statistical analyses were funded by a Commonwealth Scholarship, EU, EPSRC, Fundação para a Ciéncia e a Tecnologia (Portugal), National Institutes of Health, National Science Foundation and the Wellcome Trust.

Participating Centres

A full list of centres and authors participating in this research can be found at the Nature website.

The Wellcome Trust Case Control Consortium

The Wellcome Trust Case Control Consortium was supported by: the Medical Research Council, British Heart Foundation, Juvenile Diabetes Research Foundation, Diabetes UK, the Arthritis Research Campaign, the National Association for Colitis & Crohn's Disease and MDF The Bipolar Organisation.


Additional notes

Specific information about each disease can be found here.

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 the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.


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