Research doubles number of known genetic markers for coronary heart disease
Researchers in two international studies have discovered 17 new genetic variants linked with increased heart disease risk. The research more than doubles the known firm genetic links to coronary heart disease providing new targets and hope of developing drugs to treat this condition.
Coronary heart disease kills approximately 88,000 people in the UK every year. As well as lifestyle choices, inherited genetic variants are known to contribute to our risk of developing the disease and researchers estimate that between 30 and 60 per cent of the variability in risk between different people is down to genetic factors. The precise nature of this genetic susceptibility remains largely unknown.
The new studies – one from the CARDIoGRAM consortium and one from The Coronary Artery Disease (C4D) Genetics Consortium – use huge sets of data to look for single-letter changes in the genome that are more common in patients with coronary heart disease than in apparently healthy people.
Many of the changes point to genes that have never been previously associated with coronary heart disease. Others emphasize the role of traits that were previously known to be risk factors, such as lipid levels.
“Together, these studies reveal a far more detailed and more complex map of the genetic architecture of heart disease than we previously had access to. Our findings unmask new pathways into the disease outside the traditional heart disease risk factors.
“Importantly, these studies show that the discovered genetic risk factors for coronary heart disease are shared between populations across Europe, America and South Asia supporting a common strategy in translating such findings to treatment.”
Dr Panos Deloukas from the Wellcome Trust Sanger Institute, an author on both studies and co-leader of the C4D study
The CARDIoGRAM research involved in-depth analyses of the DNA of over 140,000 people, more than 50,000 of whom had coronary heart disease. The C4D scientists looked at the DNA of more than 70,000 people, more than 35,000 of whom had coronary heart disease.
The first study found 23 associations with coronary heart disease, 13 never seen before.
“The most exciting thing about our study – the largest ever of its type – is that we have discovered several new genes not previously known to be involved in the development of coronary heart disease. Understanding how these genes work, which is the next step, will vastly improve our knowledge of how the disease develops, and could ultimately help to develop new treatments.”
Professor Nilesh Samani of the Univeristy of Leicester who co-led the CARDIoGRAM research
Remarkably, only three of the new variants were in genes that have previously been seen in coronary heart disease. Among the other ten regions, the team identified five that were in genes involved in multiple other diseases and traits, including cerebral and abdominal aneurysm, aortic root size, celiac disease, lung adenocarcinoma, type 1 diabetes and venous thrombosis.
The C4D research looked for risk factors in European and South Asian populations. The team found five regions, which have never before been associated with coronary heart disease. One of these regions was also found in the CARDIoGRAM study.
“Our research strengthens the argument that lots of genes have a small effect on your heart disease risk, rather than a few genes having a large effect. Knowing about them will be important for directing research to find new treatments.”
Professor Hugh Watkins of the University of Oxford who co-led the C4D research
The five variants are found in genetic regions that might be involved in processes, such as lipid metabolism and the build up of fatty deposits in the arteries.
Together, the two studies go some way towards building a clearer picture of the genetic causes of coronary artery disease, pointing to important new mechanisms and routes into the disease. Unpicking these mechanisms, say the researchers, is critical in developing a more complete understanding of heart disease and identifying new therapeutic targets.
“As more and more large-scale genetic studies are carried out we are beginning to identify genetic variants that may play a significant, though small, role in the development of heart disease. These studies add 17 to the existing list. Some are plausibly associated with the development of atherosclerosis – the cause of heart attacks and strokes. Each new gene identified brings us a small step closer to understanding the biological mechanisms of cardiovascular disease development and potential new treatments.
“However, as the number of genes grows, it takes us further away from the likelihood that a simple genetic test will identify those most of risk of suffering a heart attack or a stroke.”
Professor Peter Weissberg Medical Director at the British Heart Foundation
Researchers from the two groups have now joined efforts in a global effort involving additional teams and have already found evidence to suggest that their combined data will find more genetic links to heart disease.
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The British Heart Foundation
The British Heart Foundation (BHF) is the nation’s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease.
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.
The National Institute for Health Research
The National Institute for Health Research (NIHR) provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world-class facilities (both NHS and university), conducting leading-edge research focused on the needs of patients.
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.
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