Potential of Implementing Polygenic Risk Scores in Healthcare Systems

The power of PRS in clinical care has been evidenced by genomic research and is being adopted by leading healthcare systems across the US.

It is now possible to construct a polygenic risk score (PRS) to identify how genetic variation across the genome affects your chances of developing breast cancer. Each of these variants may have a small effect, but when aggregated into a single score represent a powerful approach for assessing the genetic component of disease risk. A PRS for breast cancer can identify significant proportions of the population at heightened risk of disease. The commonly used cardiovascular disease 10-year risk estimator, the Pooled Cohort Equation, for example, is known to be less accurate in individuals with South Asian or African American ancestry. This poses a challenge when developing tests that link variation in genetics with disease risk for two main reasons. The second reason is that the frequency of both tagging and causal variants differs in different populations, so individuals can have more disease-associated variants not because of increased risk of disease but because they happen to have more of the variants. In fact, in a few cases, including breast cancer, prostate cancer, and coronary artery disease, this evidence is now sufficient that the argument is not if but when polygenic risk scoring should be incorporated into primary prevention. PRSs for these diseases, as well as few others, have similar properties: they can strongly stratify risk across ancestries, there is already some genetic testing conducted on them, and there are clear ways in which the outputs of PRS-integrated risk assessments can be used. These include increased or earlier mammographic screening for breast cancer, increased surveillance for prostate cancer, and interventions that target modifiable risk factors for cardiovascular disease. Understanding the increase in your relative risk of disease—for example knowing that your genes increase your risk by 2, 3 or 4 times the average is a common way in which the risk from non-genetic risk factors is communicated, so PRS-based recommendations can align with what patients and clinicians are already familiar with. The outputs of such risk assessments can provide individuals with an understanding of their risk of disease. Ultimately, PRSs are a tool for capturing an increasingly accurate assessment of your genetic risk of disease.