Polygenic contribution to heart disease risk highlighted

Eight percent of UK adults have the same risk of heart disease due to cumulative polygenic changes as carriers of a single rare mutation, according to a study.

Research from Genomics plc suggests that, due to the effects of many genetic changes, a significant proportion of the population has the same genetic susceptibility to heart disease as those with familial hypercholesterolemia. The study, published in PLOS One, tested the performance of the healthcare company's polygenic risk scores (PRS) in investigating previously unidentified heart disease risk in UK populations.

'What's really interesting here is that we've identified a totally different group of individuals who have the same genetic risk...' Professor Sir Peter Donnelly, founder and chief executive officer of Genomics plc, told the Times. 'Not because of a single change, rather the effects of multiple changes.'

Familial hypercholesterolemia is a monogenic condition affecting around one in 280 people that increases an individual's risk of heart disease caused by high cholesterol levels. A single mutation in one of a few key genes is enough to cause the condition to develop, and without treatment causes one in five with the condition to develop coronary artery disease by age 70.

'Familial hypercholesterolemia is an example of a condition similar to many others, like breast cancer for example, where we know that there are some high-impact mutations. If you happen to carry one, it's dangerous and it's important,' explained Professor Samuli Ripatti, from the University of Helsinki, Finland, to the Times, who was not involved in the research. 'But there's also a long trail of genetic effects that are much better-captured by polygenic risk scores. There are already hundreds and hundreds of genetic loci which have been identified to associate with cholesterol levels. So it makes sense.'

Familial hypercholesterolemia is already tested for on the NHS, and affected individuals are treated with medications to reduce cholesterol. However, this study shows that individuals with a high polygenic risk of heart disease display the same cardiovascular problems as those with the condition, leading the study authors to suggest the NHS support those with high PRS scores as well as those with rare mutations.

'Our modelling suggests that if this were added to the health check for individuals between 45 and 65 in the UK, over the next ten years it would save almost 20,000 acute events – heart attacks and strokes', Professor Donnelly continued in the Times.

Research has shown that cholesterol lowering medications such as statins are effective in reducing the risk of heart disease in those with high PRS scores, and could be prescribed to those identified by a genetic test as being at risk of heart disease. Recent NHS pilot studies have already begun to explore the possibility of including polygenic risk scores into heart disease risk assessments (see BioNews 1089 and 1167).

This study was possible due to data from the UK BioBank. However, the study authors acknowledge that their results may not be generalisable to people who are not of European ancestry. If PRSs are to be useful for more people, then this will require greater diversity in genomic datasets.