A polygenic risk score (PRS) is a numerical estimate that summarizes an individual’s genetic predisposition to certain common diseases or traits. It assesses the cumulative influence of many genetic variants across the genome, indicating an individual’s genetic likelihood of developing a particular condition.
Understanding Polygenic Risk Scores
Many common diseases, such as heart disease, type 2 diabetes, and certain cancers, are not caused by a single gene mutation. Instead, they result from the combined effect of multiple genes interacting with environmental factors, a concept known as polygenic inheritance. A polygenic risk score estimates an individual’s genetic susceptibility to such conditions, considering numerous genetic markers like single-nucleotide polymorphisms (SNPs).
It is important to distinguish PRS from tests for single-gene disorders (monogenic diseases), which are caused by a mutation in a single gene with a strong effect. Unlike a diagnosis, a PRS provides an estimate of risk or predisposition, indicating an individual’s genetic likelihood compared to others in a population. The score reflects the number of risk-increasing or risk-decreasing variants an individual possesses for a particular trait or disease.
Calculating Polygenic Risk Scores
The process of deriving a polygenic risk score involves analyzing an individual’s DNA at numerous specific points, known as single-nucleotide polymorphisms (SNPs). This analysis compares an individual’s genetic makeup to large genetic studies, specifically genome-wide association studies (GWAS). These studies identify genetic variants associated with various traits or diseases within large populations.
Each identified genetic variant contributes a small amount to the overall risk of a condition. These contributions are then summed, often weighted by their estimated effect size on the disease or trait. The resulting score indicates an individual’s genetic risk relative to a reference population.
Health Applications
Polygenic risk scores are being explored for various applications in healthcare, particularly for common complex diseases. They show promise in identifying individuals at a higher genetic likelihood for conditions like coronary artery disease, type 2 diabetes, certain cancers, and even psychiatric conditions. For instance, individuals in the top 8% of a coronary artery disease PRS distribution may have a risk comparable to those with a single-gene mutation causing familial hypercholesterolemia.
This genetic information can potentially inform personalized prevention strategies. It might guide early screening recommendations or encourage lifestyle modifications tailored to an individual’s genetic risk profile. For example, a high PRS for obesity might suggest a personalized diet. A PRS acts as a tool to complement traditional risk factors such as age, lifestyle, and family history, rather than replacing them.
Important Considerations
Polygenic risk scores provide a probability, not a definitive diagnosis, and their predictive accuracy can vary. A significant limitation is that PRS accuracy can differ across populations, largely due to a historical lack of diversity in the genetic studies used to develop these scores. As of April 2022, approximately 79% of all genome-wide association study participants were of European descent, which means scores are currently most robust for individuals of European ancestry.
The use of PRSs also raises ethical and social concerns, including potential genetic discrimination or privacy issues related to genomic data. The psychological impact of receiving risk information, especially for adult-onset conditions, also requires careful consideration. Professional genetic counseling is important for interpreting PRS results and making informed decisions, as these scores are still largely research tools. Genetic risk is only one component of disease development; environmental factors, lifestyle choices, and family medical history also play significant roles.