George Busby, Allelica CSO & Co-Founder
Allelica builds software that enables clinical genetics labs and health systems to deploy robust and accurate Polygenic Risk Scores (PRS), at scale. But what is a PRS?
In the realm of genetic medicine, geneticists have traditionally focused on single genes linked to specific diseases. But what about conditions influenced by many genes, each with a subtle effect? Enter PRSs — a powerful tool for understanding an individual’s predisposition to complex diseases.
One way to think of a PRS is as a collection of tiny tiles that form a unique mosaic of your health. Each tile represents a known genetic variant where an allele (or version of that variant) has been associated with disease risk. The color of each tile represents whether or not you have 0,1 or 2 copies of the risk allele, combined with the effect of that allele on disease risk.
By analyzing hundreds or thousands of these tiles, some of which will increase risk, and others decrease risk, we can create a single score that reflects an individual’s overall susceptibility. While a single variant might not be a dealbreaker, the cumulative sum of the effects of these variations paints a clearer picture.
PRS as a mosaic of tiles. We can translate each individual’s genotypes (rows) at 50 variants in a PRS panel (columns) into their effect on disease. Some variants have alleles that increase risk of disease in carriers (red) and others have a protective effect (blue).To build a PRS for each individual, we sum together the variant effects into a single score. Individual 7 has many risk alleles which translate into a larger PRS value (pink) than individual 2 who has more protective alleles and a much lower PRS value (green).
PRSs don’t predict guaranteed outcomes or diagnose disease. But, they do offer valuable insights for genetic counselors and physicians. They are powerful risk factors for disease which can be incorporated into risk assessments, allowing us to use this key piece of information to:
- Stratify patients: Identify individuals at higher risk for early intervention and preventive measures.
- Personalize care: Tailor screening programs and lifestyle modifications based on individual risk profiles.
- Refine research: Develop more targeted therapies by understanding the genetic architecture of complex diseases.
As genetic counselors and physicians, staying informed about PRSs is key to unlocking a new era of personalized medicine.
Are you using PRSs in your practice? What are the biggest challenges and opportunities you see?
