Advertisement

An international team led by researchers from the University of Leicester, University of Cambridge and the Baker Heart and Diabetes Institute in Australia used UK Biobank data to develop and test a powerful scoring system, called a Genomic Risk Score (GRS), which can identify people who are at risk of developing coronary heart disease prematurely because of their genetics.

People who are at high risk could be encouraged to make important lifestyle changes from an early age and be offered lifesaving medicines on a case to case basis—should they be necessary.

Genetic factors have long been known to be major contributors of someone’s risk of developing coronary heart disease—the leading cause of heart attacks.

In today's health system, doctors identify those at risk doctors use scores based on lifestyle and clinical conditions associated with coronary heart disease such as cholesterol level, blood pressure, diabetes and smoking. These scores are imprecise, age-dependent and miss a large proportion of people who appear "healthy," but will still develop the disease.

1.7 million genetic variants in a person's DNA

The big-data GRS technique takes into account 1.7 million genetic variants in a person’s DNA to calculate their underlying genetic risk for coronary heart disease. 

The team analyzed genomic data of nearly half a million people from the UK Biobank research project aged between 40 to 69 years, which included over 22,000 people who had coronary heart disease.

A powerful tool

The GRS was better at predicting someone’s risk of developing heart disease than each of the classic risk factors for coronary heart disease alone. The ability of the GRS to predict coronary heart disease was also largely independent of these known risk factors. This showed that the genes, which increase the risk of coronary heart disease, don’t simply work by elevating blood pressure or cholesterol, for example.

People with a genomic risk score in the top 20 percent of the population were over four-times more likely to develop coronary heart disease than someone with a genomic risk score in the bottom 20 percent.

In fact, men who appeared healthy by current NHS health check standards but had a high GRS were just as likely to develop coronary heart disease as someone with a low GRS and two conventional risk factors like high cholesterol or high blood pressure.

These findings help to explain why people with healthy lifestyles and no conventional risk factors can still be struck by a devastating heart attack.

Crucially, the GRS can be measured at any age including childhood as your DNA does not change. This means that those at high risk can be identified much earlier than is possible through current methods and can be targeted for prevention with lifestyle changes and, where necessary, medicines.

The GRS is also a one-time test, and with the cost of genotyping to calculate the GRS now less than $50, it is within the capability of many health services to provide.  

“At the moment we assess people for their risk of coronary heart disease in their 40’s through NHS health checks. But we know this is imprecise and also that coronary heart disease starts much earlier, several decades before symptoms develop. Therefore if we are going to do true prevention, we need to identify those at increased risk much earlier," said Nilesh Samani, medical director and professor of Cardiology at the University of Leicester who was a senior author of the study. “This study shows that the GRS can now identify such individuals. Applying it could provide a most cost effective way of preventing the enormous burden of coronary heart disease, by helping doctors select patients who would most benefit from interventions and avoiding unnecessary screening and treatments for those unlikely to benefit.” 

"The completion of the first human genome was only 15 years ago. Today, the combination of data science and massive-scale genomic cohorts has now greatly expanded the potential of healthcare," said Michael Inouye, lead author from the Baker Heart and Diabetes Institute and University of Cambridge. “While genetics is not destiny for coronary heart disease, advances in genomic prediction have brought the long history of heart disease risk screening to a critical juncture, where we may now be able to predict, plan for and possibly avoid a disease with substantial morbidity and mortality."

Today, we are just beginning to harness the enormous potential of genomic medicine. Within the next decade scientists anticipate to see this kind of technology bringing countless benefits to the lives of patients.

Advertisement
Advertisement