17 new genetic variants tied to an increased risk of coronary heart disease have emerged from two huge international research studies, more than doubling the number of known genetic links to the disease; the researchers hope their discoveries, published in Nature Genetics this week, will lead to new treatments for coronary heart disease and stroke.

A genetic variant is a piece of DNA that varies from person to person, like different spellings of the same word or phrase. A variant of a gene changes its expression, which may or may not result in obvious differences among people; for instance some variants determine eye colour, while others influence less obvious factors like risks for diseases.

One study was by the Coronary Artery Disease (C4D) Genetics Consortium and the other was from the CARDIoGRAM consortium. They were both funded by the European Union and a number of research institutions including the British Heart Foundation (BHF), the Wellcome Trust, the Medical Research Council, and the National Institute for Health Research.

In both studies, researchers scanned and compared the entire genomes of tens of thousands of people with and without coronary heart disease (also called coronary artery disease) to locate variations in DNA more likely to be found in people with the disease.

The C4D Consortium looked at the DNA of more than 15,000 people who developed coronary heart disease before they reached the age of 60. The research was co-led by researchers from the British Heart Foundation Centres of Research Excellence at the Universities of Oxford and Cambridge and Imperial College, London.

One of the C4D co-leaders is Professor Hugh Watkins of the Department of Cardiovascular Medicine at the University of Oxford.

By analysing data pooled data from discovery and replication cohorts from several genome-wide association studies for coronary heart disease, Watkins and colleagues found five genetic variants that increase the risk of coronary heart disease, including two linked to atherosclerosis, where accumulation of fatty material along the walls of arteries causes them to thicken and harden, which can cause heart attacks and strokes.

They showed that these two genetic variants might be linked to over-expression of genes, providing a starting point for understanding more about the underlying biological pathways for atherosclerosis.

Watkins said they also found that the five new variants are equally present in people from Europe and South Asia, supporting the idea that large international studies are a good way to look for genetic causes of heart disease.

Watkins told the press that:

“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.”

The CARDIoGRAM consortium, involving 67 clinicians and scientists from UK, Europe, Iceland, USA and Canada, and led by Professor Nilesh Samani of the University of Leicester, looked at the DNA of more than 140,000 people, including over 50,000 with coronoary heart disease.

Samani and colleagues pooled data from 14 genome-wide association studies of coronary heart disease followed by replication in additional cohorts. They confirmed 10 previously known variants and identified 13 new ones linked to the disease.

Samani told the press that:

“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.”

Samani and colleagues also noted that of the 13 new variants, five appear to have “pleiotropic effects”, that is they showed strong links with other human diseases and traits.

Members of the two consortia now plan to work together. And according to a BHF statement, it appears they have already found evidence to make them think combining their data will reveal further genetic links to heart disease.

BHF medical director Professor Peter Weissberg said:

“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.”

“Each new gene identified brings us a small step closer to understanding the biological mechanisms of cardiovascular disease development and potential new treatments”, said Weissberg.

But, he also warned, that as the list of genes linked to coronary heart disease grows, the chances of developing a simple test to identify those people most at risk become more remote.

“A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.”
The Coronary Artery Disease (C4D) Genetics Consortium.
Nature Genetics. Published online: 06 March 2011.

“Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.”
Heribert Schunkert, Inke R König, Sekar Kathiresan, Muredach P Reilly, Themistocles L Assimes, Hilma Holm, Michael Preuss, Alexandre F R Stewart, Maja Barbalic et al, and Nilesh J Samani for the CARDIoGRAM Consortium.
Nature Genetics. Published online: 06 March 2011.

Additional source: British Heart Foundation, University of Leicester, (press statements, 6 Mar 2011).

Written by: Catharine Paddock, PhD