A scoring system that predicts whether a person will develop a disease based on their genes performs poorly when it comes to population screening for common conditions such as breast cancer and heart disease, according to researchers.
Polygenic risk scores estimate the likelihood of a person developing a disease based on genetic variants.
A team led by University College London (UCL) explored how risk scores perform alongside conventional screening methods.
For the study, published in the journal BMJ Medicine, researchers assessed 926 polygenic risk scores for 310 diseases.
Using data from the Polygenic Score (PGS) Catalog, they determined the detection rate and the rates of false positives if the scores were used in screening.
When held to the same standards as employed for other tests in medicine, polygenic risk scores performed poorly for prediction and screening across a range of common diseases— Prof Aroon Hingorani
The team found that only 11% of people who develop disease are identified by polygenic risk scores, while 5% of those who do not fall ill are false positives.
Lead author Prof Aroon Hingorani, of the UCL Institute of Cardiovascular Science, said: “Strong claims have been made about the potential of polygenic risk scores in medicine, but our study shows that this is not justified.
“We found that, when held to the same standards as employed for other tests in medicine, polygenic risk scores performed poorly for prediction and screening across a range of common diseases.”
For breast cancer, the risk score identified only 10% of eventual cases, along with 12% of cases of coronary artery disease.
Co-author Professor Sir Nicholas Wald, of the UCL Institute of Health Informatics, added: “It has been suggested that polygenic risk scores could be introduced early on to help prevent breast cancer and heart disease but, in the examples we looked at, we found that the scores contributed little, if any, health benefit while adding cost and complexity.”
Dr Jasmine Gratton, of the UCL Institute of Cardiovascular Science, said polygenic risk scores “seem attractive because genotyping is now inexpensive, the same for all diseases and is performed only once because a person’s genotype does not change”.
Our results build on evidence that indicates that polygenic risk scores do not have a role in public health screening programmes— Prof Sir Nick Wald
However, she added that “these features are irrelevant if the test is not useful”.
Prof Sir Nick Wald said: “Our results build on evidence that indicates that polygenic risk scores do not have a role in public health screening programmes.”
However researchers stressed that polygenic risk scores should not be confused with genetic testing for certain mutations, such as BRCA1 and BRCA2, which are vital in screening for breast and ovarian cancer.
They also emphasised that discovering genetic variants associated with disease risk is “still crucial for drug development”.
Dusko Ilic, a professor of stem cell sciences at King’s College London (KCL), said: “It comes as no surprise to me that polygenic risk scores have shown poor performance in population screening, individual risk prediction, and population risk stratification.
“They overlook the significant impact of epigenetic regulation and the environment on an individual’s overall health.
“Reports like this one serve as a necessary reality check to be wary around exaggerated claims surrounding the influence of polygenic risk scores on healthcare and health outcomes. This applies to both individuals and healthcare professionals.”
The current paper generally takes a narrow view of how polygenic scores can be used— Prof Michael Inouye and assistant Prof Sam Lambert
However, Prof Michael Inouye and assistant Prof Sam Lambert of the University of Cambridge, who were lead authors of the PGS Catalog which was looked at in the study, said the system has “potential utility in many different clinical use cases”.
“Hundreds of papers from research groups around the world have demonstrated this,” they added.
“The current paper generally takes a narrow view of how polygenic scores can be used.”
They said other studies use the system “in more flexible ways”.
“For example those that vary the interval and age of screening initiation of cancer screening do show potential public health benefits and indeed cost-effectiveness of PGS,” they added.
“Similar results have been seen for cardiovascular disease. Considering the extensive literature on PGS, it does now look like there is ample evidence for ramping up translational studies of polygenic scores, including pragmatic trials.”
The UCL study was supported by the British Heart Foundation, UK Research and Innovation (UKRI), National Institute for Health and Care Research (NIHR), and the NIHR Biomedical Research Centre at UCLH and UCL.
