Episode 71: Understanding Your Risk with a PRS

This month, TGen Talks explores polygenic risk scores with Dr. David Duggan, an associate professor in the Quantitative Medicine and Systems Biology Division at TGen. A polygenic risk score is a number that indicates the combined effect of many genetic variants on a person's risk of developing a certain trait or disease. Each genetic variant adds a small amount to the overall risk. When these small effects are added together, they help predict the likelihood of developing the trait or disease.
    Think of the human genome as a deck of cards, where each card represents a different genetic variant. The value of each card represents the risk contribution of that variant. For example, an Ace might represent a high-risk variant (4 points), while a 2 might represent a low-risk variant (1 point). Let's assume all contributions are positive for simplicity, although in reality, some variants might reduce risk.
    Imagine drawing 10 cards from the deck randomly. These 10 cards represent the genetic variants you inherited from your parents. Each card has a point value (risk contribution). Adding up the points of the 10 cards gives you your polygenic risk score. This score indicates your genetic predisposition to the trait or disease. You can then compare this score against population averages or thresholds to determine if you are at higher or lower risk for the trait or disease.
    In this analogy, each card represents a genetic variant, and its point value represents its contribution to your overall genetic risk for a specific trait or disease. The polygenic risk score is the sum of these contributions, much like summing the values of drawn cards to get a total score. This information can help you and your doctor make informed health decisions, such as focusing on preventive measures. Dr. Duggan notes that lifestyle factors also play a significant role in disease risk, sometimes reducing genetic risk by up to 50%.
Whether you’re a healthcare professional, a genetics enthusiast, or just curious about the future of personalized medicine, this month’s TGen Talks is worth the listen.