Genetic predisposition research

'It runs in the family'

For many families across the UK, history repeats itself over and over, with loved ones from every generation being lost to heart attacks.

Even if we make heart healthy choices, the DNA we inherit from our parents plays a major role in determining our risk of heart disease.

That’s why some families are blighted by heart attacks. Their DNA – inherited through the generations – contains subtle variations that mean their coronary arteries are more prone to disease.

Our BHF-funded scientist are working on identifying the genes that increase our risk of developing heart and circulatory diseases.

Read more about coronary heart disease.

Genetic predisposition research today

We’ve funded major studies to discover which DNA variations are linked to high blood pressure and a number of other conditions including atherosclerosis which causes conditions such as coronary heart disease, peripheral artery disease and is the main cause of stroke. Now, we’re supporting researchers to take the next steps towards the eventual goal of personalised medicine to help families whose genes leave them at the greatest risk.

The culprit on chromosome 9

Research has shown that variations in DNA at one position on chromosome 9 – known as chr9p21 – significantly raise the risk of coronary heart disease. We’re funding Professor Mallat at the University of Cambridge to tease out exactly how it has this effect. He’s discovered this DNA variation leaves blood vessels vulnerable to inflammation - a key process in the development of coronary heart disease. This is an exciting clue and we’re now supporting him to take this finding further, and carefully decipher all the molecular steps in this process.

The next step will be to identify which parts of the process new medicines can be aimed at. In the future, if doctors know a family carries the risky variation at chr9p21, they may be offered precision medicines to stop heart disease in its tracks.

Suspects under investigation

The human genome – the complete set of DNA in each human cell – is so vast that searching for tiny variations linked to heart disease is like searching for a needle in a field full of haystacks.

But we’re not searching by hand, and the technology available for researchers to analyse genomes has advanced so much in a short time that new regions of DNA with important variations are still being discovered at pace.

However, that’s just the first step. Now we’re funding Professor Panos Deloukas and his team at Barts and the London School of Medicine and Dentistry to find out more about the regions of DNA that have been identified by recent genome analyses. Do they contain genes? If so, what do they do? Do they produce molecules that could be measured in a simple test for heart attack risk?

By drilling down into the results of genome studies, we’ll find new ways to combat the risk passed down in our DNA through generations.

The difference we’ve already made

In the late 1990s, the BHF – in partnership with the Medical Research Council – funded the largest genetic study of families affected by premature heart disease of its time. The Family Heart Study took blood samples from 4,000 volunteers, and created a DNA database with this vital information.

Since then, this database has been combined with others, to create a massive collection with much greater power to detect the tiny DNA variations that matter. One such important variation found in this database is chr9p21, which can increase the risk of heart disease by up to 50 percent. It’s the subject of Professor Mallat’s BHF-funded research above.

Researchers all over the world are building on the clues revealed by the genome studies made possible by the BHF/MRC Family Heart Study and others like it. With their expertise, we’ll beat the heartbreak caused by premature deaths from heart and circulatory disease in families whose DNA is putting them at risk.

Read more about our successes in genetic predisposition research.