06 March 2011

Research doubles number of known genetic markers for coronary heart disease

Researchers analyse more than 200,000 individuals to unmask 17 heart disease DNA variants

Researchers in two international studies, from the CARDIoGRAM and The Coronary Artery Disease (C4D) Genetics Consortia, 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 and gives hope of developing new treatments for coronary heart disease and strokes.

Researchers in two international studies, from the CARDIoGRAM and The Coronary Artery Disease (C4D) Genetics Consortia, 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 and gives hope of developing new treatments for coronary heart disease and strokes. [Gordon Museum, Wellcome Images]

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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," says Dr Panos Deloukas, from the Wellcome Trust Sanger Institute, an author on both studies and co-leader of the C4D study. "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."

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," said Professor Nilesh Samani of the Univeristy of Leicester, who co-led the CARDIoGRAM research. "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."

" 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. "

Dr Panos Deloukas

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," says Professor Hugh Watkins of the University of Oxford, who co-led the C4D research. "Knowing about them will be important for directing research to find new treatments.

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," said Professor Peter Weissberg, Medical Director at the British Heart Foundation. "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."

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.

Notes to Editors

Publication details

Coronary Artery Disease (C4) Genetics Consortium study:

  • A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.

    Coronary Artery Disease (C4D) Genetics Consortium

    Nature genetics 2011;43;4;339-44

CARDIoGRAM Consortium study:

  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

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    Nature genetics 2011;43;4;333-8

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