For more than three decades Professor Sir Nilesh Samani has been at the forefront of research investigating the inherited basis of common cardiovascular diseases. These diseases include high blood pressure (hypertension) and coronary artery disease, the cause of angina and heart attacks.
Professor Samani’s ambition has been to truly comprehend why these diseases occur more commonly in some families but not others. This not an easy task as they have a substantial but complex genetic architecture requiring sophisticated deciphering.
By assembling some of the best clinical cohorts for his research, such as the British Heart Foundation Family Heart Study (BHF-FHS) and the Genetic Regulation of Arterial Pressure in the Community study (GRAPHIC), and working with national and international collaborators, Professor Samani has led efforts using the latest technologies to discover genetic changes in an individual’s DNA that increase their risk of heart disease.
Several hundreds of these changes have now been successfully identified, which has revolutionised our understanding of the causes of heart disease.
Professor Samani’s discoveries have major potential implications for science, development of new treatments, clinical practice, and patients. The new genes identified that affect the risk of developing coronary artery disease or hypertension offer opportunities to develop new treatments to tackle these major diseases. Professor Samani’s team have dissected the underlying mechanisms by which some of these genes affect risk, thereby helping this translation.
The discoveries have also had a profound impact on how the pharmaceutical industry prioritises their targets for drug development. Previously, they relied on observational and other more circumstantial evidence, which can sometimes be misleading. Now, they put much more emphasis on having genetic evidence of the type provided by Professor Samani’s research before embarking on a costly drug development programme.
Predicting and preventing
A potential benefit of equal, if not greater importance, arising from Professor Samani’s ground-breaking research, is the ability to identify people who are at increased risk before they develop the disease so that prevention measures can be initiated, halting the disease occurring at all.
Individually, each of the changes in DNA that his research has uncovered only has a small effect on risk but when combined into a genetic risk score (often called a polygenic risk score, PRS), this can partition individuals into very different lifetime trajectories of risk.
As Professor Samani explains: “A polygenic risk score is like the cards you are dealt with from a large deck, determined by which DNA changes your parents carry. Some people will, by chance, carry a lot of risk cards and others very few. We have shown, for example, that this can change an individual’s risk of developing coronary artery disease by a factor of three- or four-fold or more and that information on PRS adds to current clinical assessment of risk."