A new approach in personalised medicine aims to use genomics to improve risk prediction for cardiovascular disease
The new tool will add genomic information to the combination of factors that doctors already consider when assessing a patient’s chance of developing the condition.
What are polygenic risk scores?
Heart disease, like many common diseases, is frequently the result of multifactorial inheritance. This means that rather than being caused by a single gene variant, it is caused by many different genetic variants, in addition to environmental factors.
Although these variants can have seemingly insignificant effects when considered individually, when taken together they can make a substantial difference to an individual’s chance of developing the condition.
Polygenic risk scores are a way to measure and quantify the effects of many gene variants on an individual’s phenotype. In other words, they estimate a person’s predisposition to a certain condition or trait based on genetic variants throughout the genome. You can learn more about polygenic risk scores in our article.
The study aims to combine this type of polygenic risk score with clinical risk scores to provide a clearer picture of who may develop heart disease.
How will the tool work?
The integrated risk tool was developed by Genomics plc, a company that evolved out of genomics research undertaken at the University of Oxford.
Around 1,000 patients in the North East of England will be given the opportunity to participate in the trial by giving blood samples during routine GP appointments.
DNA from the samples will be analysed and over one million datapoints will be combined into a genetic risk score. That score will then be combined with traditional markers such as cholesterol levels and BMI to generate an overall risk score.
“This represents a real first in personalised medicine. By using genetics we can improve risk prediction for cardiovascular disease so that therapies like statins, as well as lifestyle changes, can be better targeted to the right individuals,” said Genomics plc CEO Professor Sir Peter Donnelly.
The clinical use of polygenic scores is not without controversy. They are widely accepted to be very accurate at population level, but their applicability for predicting disease in individuals is less clear.
A 2019 report published by the PHG Foundation concluded that “there is currently no evidence for the clinical utility of PRS for cardiovascular disease prevention but this in itself does not mean that such evidence may not emerge in future years. Rather it may reflect the absence of a purpose or clear clinical application for PRS, at this stage.”
As such, pilot studies such as this one will be important as they can gather evidence about whether polygenic risk scores can lead to interventions that ultimately save lives. If this trial is successful, the same approach could be used in future for other common conditions, such as diabetes and some cancers.
The importance of equity
Another reason polygenic risk scores can be controversial is that they are created from findings of genome-wide association studies and, therefore, can be limited in their applicability depending on the diversity of the initial dataset. Because many genomic datasets contain genomes predominantly from people of European ancestry, results derived from them can be less useful for people of other ethnicities, as explained by bioinformatician Nana E. Mensah in our recent article.
However, the screening approach that will be trialled in the NHS can “more accurately predict the risk of cardiovascular disease across multiple ancestries and ethnicities,” according to results published in the American Journal of Cardiology.
“Differential performance of clinical tools across diverse groups remains a major issue. No ancestry or ethnic group should be disadvantaged by the use of any clinical tool, nor indeed be disadvantaged by the lack of its use,” said Professor Sir Donnelly. “To our knowledge, this is the first time, for any disease, that an integrated risk tool combining a current clinical tool and polygenic risk scores has been successfully validated across multiple ethnicities and ancestries.”
More information about the trial can be found on the Genomics plc website.