Researchers set to find 'genetic signposts' for eight diseases

The Wellcome Trust Case Control Consortium (WTCCC)

One of the biggest projects ever undertaken to identify the genetic variations that may predispose people to or protect them from eight major diseases is to begin after receiving almost £9 million of funding from the Wellcome Trust.

The Wellcome Trust Case Control Consortium (WTCCC) is a collaboration of 24 leading human geneticists, who will analyse thousands of DNA samples from patients suffering with different diseases to identify common genetic variations for each condition. It is hoped that by identifying these genetic signposts, researchers will be able to understand which people are most at risk, and also produce more effective treatments.

The WTCCC will search for the genetic signposts for tuberculosis, coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn’s disease and ulcerative colitis, bipolar disorder and hypertension. The research will be conducted at a number of institutes throughout the UK, including the Wellcome Trust Sanger Institute, Cambridge University and Oxford University.

Researchers will analyse over 19,000 DNA samples – two thousand patients for each disease and three thousand control samples – searching for important genetic differences between people who do and don’t have each disease.

“To treat a disease effectively, we need to understand it. If we can identify the common genetic triggers for these diseases, it will give us a foothold in the biological cycle and leave us better situated to fully understand what happens with each of these diseases and who may be more likely to get them.”

“This should open the door for us to develop better diagnostic tests and also help in developing more effective treatments.”

“A single disease has never been subject to such level of intense genetic analysis. The fact that we’re looking at eight underlines the significance of this programme and the progress being made in this field.”

Professor Peter Donnelly from the Department of Statistics at Oxford, who chairs the consortium

Although the human genome is made up of more than three billion chemical bases, researchers now know that most of these are identical in everyone. This project will examine 675,000 points where key variations occur.

“The Human Genome Project generated the foundation to catalogue common sequence variation whereas efforts such as HapMap are converting this information to a comprehensive set of genetic markers that allows us to scan the genome for susceptibility to disease. It is exciting and rewarding to see that we now have the necessary tools and collections in hand to investigate the genetics of common diseases.”

Dr Panos Deloukas of the Wellcome Trust Sanger Institute

As a second project The WTCCC will also analyse 15,000 polymorphic markers that alter protein sequence to look for genetic variations relating to another four diseases – breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis.

“This groundbreaking project is possible because of the sequencing of the human genome. It is an excellent illustration of the importance of knowing the human genome sequence and cataloguing its variations. Hopefully, with the insight gained into these diseases we will be able to make real progress in combating them.”

Dr Mark Walport, Director of the Wellcome Trust

The projects begin immediately and will take around three years to complete.

More information

1. TB killed 1.75 million people worldwide in 2003 – World Health Organisation.
2. Coronary Heart Disease is the UK’s biggest killer accounting for 114,000 deaths in 2003 – British Heart Foundation.
3. 1.8 million people in the UK live with diabetes – Diabetes UK
4. 387,000 people in the UK have rheumatoid arthritis – Arthritis Research Campaign.
5. 60,000 people in the UK have Crohn’s Disease – National Association for Colitis and Crohn’s Disease
6. Bipolar mood disorders affect around 3 per cent of the population world-wide, many of whom die by suicide – International Society for Bipolar Disorders.
7. High blood pressure affects over 16 million people in the UK – The Blood Pressure Association
8. The UK 1958 Birth Cohort together with the UK Blood Services of England, Scotland and Wales will provide 3000 samples from healthy controls. The contribution by the UK Blood Services is made possible because every day 11,000 people give a blood donation to help save lives of NHS patients. As part of their routine donation, a small sample will be taken for the WTCCC.
9. The International HapMap Project is a multi-country effort to identify and catalogue genetic similarities and differences in human beings. Using the information in the HapMap, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors. The Project is a collaboration among scientists and funding agencies from Japan, the United Kingdom, Canada, China, Nigeria, and the United States. All of the information generated by the Project will be released into the public domain.

Principal Investigators for WTCCC are:

• Professor Matthew Brown – Institute of Musculoskeletal Sciences, University of Oxford.
• Professor Lon Cardon – Wellcome Trust Centre for Human Genetics, Oxford.
• Professor Mark Caulfield – William Harvey Research Institute, London.
• Professor David Clayton – JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research.
• Professor Alastair Compston – Department of Clinical Neurosciences University of Cambridge.
• Professor Nick Craddock – Department of Psychological Medicine, University of Wales College of Medicine.
• Dr Panos Deloukas – The Wellcome Trust Sanger Institute, Cambridge.
• Professor Peter Donnelly – Department of Statistics, University of Oxford.
• Professor Martin Farrall – Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, Oxford.
• Dr Stephen Gough – University of Birmingham.
• Professor Alistair Hall – Institute for Cardiovascular Research, Leeds General Infirmary.
• Professor Andrew Hattersley – Diabetes and Vascular Medicine, Peninsula Medical School,
• Professor Adrian Hill – The Wellcome Trust Centre for Human Genetics, Oxford.
• Dr Dominic Kwiatkowski – The Wellcome Trust Centre for Human Genetics, Oxford.
• Professor Mark McCarthy – Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM).
• Professor Christopher Mathew – Department of Medical and Molecular Genetics, Guy’s Hospital, London.
• Dr Willem Ouwehand – Department of Haematology, University of Cambridge & National Blood Service Cambridge.
• Dr Miles Parkes – Gastroenterology Unit, Addenbrooke’s Hospital, Cambridge.
• Dr Miles Parkes – Gastroenterology Unit, Addenbrooke’s Hospital, Cambridge.
• Professor Marcus Pembrey – ALSPAC Director of Genetics.
• Dr Nazneen Rahman – Institute of Cancer Research.
• Professor Nilesh Samani – Department of Cardiovascular Sciences, University of Leicester.
• Professor Michael Stratton – The Wellcome Trust Sanger Institute, Cambridge.
• Professor John Todd – Wellcome Trust Sanger Institute, Cambridge & University of Cambridge.
• Dr Jane Worthington – School of Epidemiology & Health Sciences, The University of Manchester.