UK scientists lift lid on genetics of coronary artery disease
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Scientists have moved a step closer to understanding how our genetic make-up can lead us to develop heart disease and to predicting who is most at risk. In a study published today, they have confirmed six new genetic variants that increase the likelihood of developing coronary artery disease. Heart disease is the UK’s largest killer, accounting for 105,000 deaths annually.
The research, jointly carried out by researchers at the University of Leicester and the University of Leeds, in collaboration with colleagues in Germany at the Universities of Lubeck and Regensburg, is published online today in the journal New England Journal of Medicine.
The first important clues to the identities of these variants came from a genome-wide analysis conducted in almost 2,000 people with coronary artery disease and 3,000 healthy controls as part of the Wellcome Trust Case Control Consortium (WTCCC), the largest ever study of the genetics of common disease. The findings were then compared with the German MI Family Study, with almost 900 addition cases and 1600 additional controls.
The results coincide with the announcement that the WTCCC has been awarded a further £7.7 million to investigate in detail the genes that have been identified already. The Wellcome Trust has also put out a call to widen its scope to study other common diseases.
The researchers found that changes in our DNA on chromosomes 2, 6, 10 and 15 and two on chromosome 1 were associated with increased risk of developing coronary artery disease and heart attacks The study also confirmed the importance of a variant on chromosome 9, previous identified in an independent study.
“We are not talking about rare genetic variants here, but rather variants that are very common in our population,” says Professor Nilesh Samani, British Heart Foundation Chair of Cardiology at the University of Leicester, and lead author on the paper. “Many of these genetic variants are carried by between a quarter and three-quarters of white Europeans. They are clearly very important and explain a significant proportion of the heart attacks that occur.”
Genetic information is inherited from each parent and may include variants that influence the likelihood of developing disease. Carrying one copy of the newly-identified variants increases the chances of developing heart disease by at least 20 per cent; carrying two such copies would increase the risk by over 40 per cent. A person who carries copies of more than one of the genetic variants may be at a substantially higher risk, therefore.
“Understanding the genetics that lead to heart disease is a powerful tool to tell us how much risk a person faces,” says Professor Samani. “However, it’s important to emphasise that even if a person carries one or more of the risk variants, they can still do a lot to reduce their risk by adopting a healthy lifestyle, not smoking and if they have High Blood Pressure or raised cholesterol levels, to have these treated.”
Although the researchers know that some of the variants implicated are involved in cell growth and cell division, they are now working to understand exactly how this leads to heart disease.
“We still don’t know the whole story, but these findings are an important step along the way to understanding what causes heart disease,” says Professor Alistair Hall from the University of Leeds, also a co-author of the study. “Heart disease is a complex disease, involving a number of genetic variants, many which until now had not been thought to be implicated in heart disease.”
The findings have been welcomed by Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, which part-funded the study.
“Discovering new genetic variants shows how powerful these exciting studies are,” says Professor Pearson. “We can now examine the whole genome quickly to produce great results - something that couldn’t have been done at all a few years ago. This study demonstrates just how important it is to invest in a healthy lifestyle to help protect your heart, especially if you think your family history might put you at increased risk of heart disease.
“Our thanks go to this dedicated research team and the thousands of heart patients, who provided samples of their DNA for the BHF’s Family Heart Study, which made this research possible. We now look forward to seeing further research so we can add more pieces to this complex puzzle.”
The £9 million WTCCC, which announced its initial findings in June, is one of the biggest studies ever undertaken to identify the genetic variations that predispose people to or protect them from major diseases. It looked at bipolar disorder, Crohn’s disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes.
Today, the Wellcome Trust has announced a further £7.7 million for the study to continue and analyse in more depth the initial findings. The Trust, the UK’s largest medical research charity, has also called for proposals from scientists to study other common diseases.
“This is an exciting step forward,” says Dr Mark Walport, Director of the Wellcome Trust. “We now need to understand how these common genetic variants cause increased risk of heart disease. From this understanding, we may be able to develop new preventative strategies and new treatments.”
Contact: Craig Brierley
44-207-611-7329
Wellcome Trust
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