Polygenic Risk Scores

Genetic tests to determine risk for monogenic diseases (such as cystic fibrosis or Huntington’s Disease) that are caused by a single mutation have been in use for over a decade. However, determining risk for complex diseases, which can be caused by hundreds to thousands of genetic variants that act in conjunction with environmental factors, remains challenging.

Polygenic risk scores (also known as polygenic scores and genetic risk scores) represent the total number of genetic variants that an individual has to assess their heritable risk of developing a particular disease. While there is still much more work needed to realize the potential for polygenic risk scores in precision medicine, polygenic risk scores have the potential to impact complex disease research and healthcare in a variety of ways:

• Assess an individual's risk of disease
• Analyze populations based on disease risk
• Select samples within cohorts for further analysis

What Are Polygenic Risk Scores?

Polygenic risk scores can provide researchers and physicians valuable insight into how predictive biomarkers for a specific complex disease can stratify patient populations according to risk. A study published by Khera, et al. in 2018 examined genome-wide polygenic risk scores in a population of over 250,000 individuals in the UK Biobank.¹ They found 8% of the population tested had polygenic risk scores that conferred ≥ threefold increased risk for coronary artery disease.

This is a great example of how polygenic risk scores can be used by clinicians to stratify patients according to risk and identify individuals who would most benefit from additional monitoring or early preventative measures to offset the risk of disease.