Genetics and stem cells

Genetic link to heart disease

A clutch of gene variants that raise the risk of heart disease have been identified by researchers, the Daily Mail said. The paper reported that six common gene defects had been discovered which link to an increased risk of a heart attack: “Carrying two copies of three of the genes raises a person’s risk of heart disease by 78% – the equivalent of being a heavy smoker.” A greater understanding of the genetics behind the condition might “lead to new ways of treating and even preventing heart disease”, it explained on 19 July 2007.

It remains to be seen if any new diagnostic or predictive approaches for coronary artery disease result from this study or how much the untangling of the genetic basis of these disorders will add to our current knowledge; we already know that a strong family history of an early heart attack in a close relative is a heart disease risk factor.

Where did the story come from?

The story was based on research conducted by Nilesh Samani and members of the Wellcome Trust Case Control Consortium and was funded by a grant from the Wellcome Trust. It was published in one of the top 10 peer-reviewed medical journals, New England Journal of Medicine

What kind of scientific study was this?

Researchers used data from a genome-wide association study, a type of case-control study, conducted by the Wellcome Trust Case Control Consortium (WTCCC) which was originally set up to look for associations between particular gene sequences (variants) and seven complex diseases.

The researchers used the data to assess the association between certain gene variants and coronary artery disease. Data from a similar study in German people who had a heart attack was used to to check whether any potential associations were also shown in the German population. 

In both studies, people who had a history of heart disease were compared with people who had no history of heart disease. In the WTCCC study, the researchers recruited 1,988 people with a history of coronary heart disease (either a heart attack or heart surgery) and a strong family history of coronary artery disease (cases); they also recruited a total of 3,462 people who did not have heart disease (controls). In the German study, researchers recruited 875 people who had a heart attack before the age of 60 and had at least one relative with coronary artery disease (cases); they also recruited 1,644 people who had no heart disease (controls).

What were the results of the study?

A detailed analysis, using complex statistical methods, of the nearly 400 genetic variants that seemed to be associated with coronary artery disease in the WTCCC study, led to the conclusion that nine were likely to be true associations. The researchers then checked whether these genetic associations were evident in the people who took part in the German study. They found that variants in three main areas – on chromosomes 9, 6, and 2 – were also associated with heart disease in the German study.

The researchers estimated that about 38% of cardiovascular disease could be explained by variants in these regions. The variant on chromosome 9 was the most strongly associated with heart disease. They found that adding a measure of the three genetic variants identified in this study to the usual method of assessing risk for heart disease (based on the Framingham risk score) increased its ability to predict how likely a person will be to get heart disease.

What interpretations did the researchers draw from these results?

The authors concluded that they had identified several areas of the genome that “substantially affect the risk of development of coronary artery disease”.

What does the NHS Knowledge Service make of this study?

The study seemed well-conducted, and the results are reliable. It is a large study and the researchers have checked their associations in a second population, which increases our confidence that these variants are truly associated with an increased risk of heart disease. 

  • We note that little is known about the biological basis behind this increase in risk. 
  • A very high proportion (more than 70%) of people in both studies had high cholesterol or were smokers. 
  • The estimate of what proportion of heart disease could be explained by the genetic variants in this population may be higher than the percentage in the general population. This is because the people in this study all had a family history of heart disease. There is a well-known inherited predisposition to heart disease, therefore before a new method of testing is accepted we need to know how much better testing is than simply asking people if they have a family history of the condition.

Although testing for these genetic variants in the future may increase our ability to predict who might be at higher risk of heart disease, it also remains to be seen whether people who find out that they are at increased risk for genetic reasons would maintain healthier lifestyles.

This study increases our understanding of the reasons why some people are more likely to get heart disease than others .

Sir Muir Gray adds…

Everyone in the United Kingdom is at risk of heart and other vascular diseases. Some people who have a condition called familial hypercholesterolaemia are at very, very high risk. These people are usually identified by testing the relatives of people who have a heart attack early, for example at the age of 40 or 45.

These newly identified variants may help identify people at very high risk in the general population. This, however, can already be done using the risk factors we know about, such as smoking or high blood pressure. More research on the use of these latest genetic markers in heart disease prevention is necessary before the health service can use this knowledge.

Even if you do not have any of these risk factors, vascular disease is still a risk; everyone is at risk whatever their genes.

NHS Attribution