Scientists lift lid on genetics of coronary artery disease
Largest ever genetic study receives £7.7 million boost
22.00 18 July 2007
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 2000 people with coronary artery disease and 3000 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, previously 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 one-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 (BHF), 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
Media Officer
Wellcome Trust
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Notes for editors
1. Samani N J et al. Genome-wide association analysis of coronary artery disease. New England Journal of Medicine – published in advance online on 18 July 2007.
2. Jpeg images of Professor Samani available - email pressoffice@le.ac.uk.
3. 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.
4. The British Heart Foundation is leading the battle against heart and circulatory disease – the UK's biggest killer. The charity is a major funder and authority in cardiovascular research. It plays an important role in funding education, both of the public and of health professionals, and in providing life-saving cardiac equipment and support for rehabilitation and care.
5. The University of Leicester is a member of the 1994 group of universities that share a commitment to research excellence, high-quality teaching and an outstanding student experience.
- Ranked joint top for two consecutive years for the quality of teaching and overall satisfaction among full-time students at English universities.
- Ranked as a top 20 university by 'The Times Good University Guide' and the 'Guardian University League Table'.
- One of just 19 UK universities to feature in world's top 200 - Shanghai Jiao Tong International Index, 2005 and 2006.
- Short-listed Higher Education Institution of the Year - THES awards 2005 and 2006
- Students' Union of the Year award 2005, short-listed 2006
Founded in 1921, the University of Leicester has 19 000 students from 136 countries. Teaching in 18 subject areas has been graded Excellent by the Quality Assurance Agency - including 14 successive scores - a consistent run of success matched by just one other UK University.
Leicester is world renowned for the invention of DNA fingerprinting by Professor Sir Alec Jeffreys and houses Europe's biggest academic Space Research Centre. Around 90 per cent of staff are actively engaged in high-quality research and 13 subject areas have been awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level. The University's research grant income places it among the top 20 UK research universities. The University employs over 3000 people, has an annual turnover of £173 million, covers an estate of 94 hectares and is engaged in a £300m investment programme - among the biggest of any UK university.
6.
University of Leeds
With over 33 000 students, the University of Leeds is the second largest in the UK and has a strategic ambition to become one of the top 50 universities in the world by 2015. The vision is shared by its Faculty of Medicine and Health, whose research excellence is spread across a number of schools and institutes whose key theme is the translation of innovative scientific development into clinical practice. With over £100m of current research grants and contracts, a third of which are from UK industry and Government sources, the faculty is a major international player in research covering a broad spectrum from lab-based investigations to applied clinical research and the public health sciences. The faculty's research excellence informs teaching and learning with students having access to academics at the forefront of thinking in their field.
7. The following institutions were involved in the study: University of Leicester; University of Leeds; University of Cambridge; National Health Service Blood and Transplant, Cambridge; the Wellcome Trust Sanger Institute (UK); Universität zu Lübeck; Universität Regensburg; GSF–Nationales Forschungszentrum für Umwelt und Gesundheit; Technische Universität München; Ludwig Maximilians University; Johannes Gutenberg University Mainz, Germany; Université Pierre et Marie, France.
8. Supported by grants from the Wellcome Trust, the National Genome Research Network 2 of the German Federal Ministry of Education and Research, and the Cardiogenics project of the European Union. Recruitment for the WTCCC study was supported by grants from the British Heart Foundation and the Medical Research Council, and recruitment for the German MI Family study was supported by grants from the Deutsche Forschungsgemeinschaft and the Deutsche Herzstiftung. Support was also received from the Wellcome Trust Functional Genomics Initiative in Cardiovascular Genetics and the KORA (Cooperative Research in the Region of Augsburg) research platform of the GSF–National Research Centre.