May 17, 2025
In the evolving field of genomics, a polygenic risk score (PRS) is a powerful tool for predicting an individual's susceptibility to various complex diseases, including pulmonary diseases and asthma. By aggregating the effects of numerous genetic variants, a PRS provides a comprehensive estimate of genetic predisposition, offering valuable insights for personalized medicine.
These scores are calculated by totaling the effects of multiple genetic variants, each contributing a small amount to the overall risk of developing a particular disease. Unlike single-gene disorders, which are influenced by mutations in a single gene, complex diseases such as asthma and other pulmonary conditions are influenced by many genetic factors, each with a modest effect. The PRS captures this complexity, providing a more nuanced risk assessment.
Victor E. Ortega, M.D., Ph.D., a pulmonary disease specialist and genetic epidemiologist at Mayo Clinic in Phoenix, Arizona, discusses how PRSs estimate the overall risk someone has of getting a disease by adding up the small effects of variants throughout an individual's entire genome on Tomorrow's Cure, a podcast where an award-winning journalist facilitates conversations between experts from Mayo Clinic and renowned organizations. He says, "Imagine knowing your genetic predisposition for developing severe asthma or chronic obstructive pulmonary disease (COPD) based on data from your whole genome. With this knowledge, you could make informed lifestyle choices and receive enhanced screenings to mitigate that risk."
Clinical applications and benefits
The clinical applications of PRSs are vast and promising. By integrating PRSs into routine clinical practice, healthcare professionals can identify people at high risk of specific diseases early on, enabling proactive interventions. For instance, individuals with a high PRS for asthma might benefit from more-frequent respiratory assessments and tailored lifestyle modifications to reduce their risk.
Moreover, PRSs can enhance the precision of existing risk models. Traditional risk factors such as age, family history and lifestyle are important, but they do not capture the full genetic landscape. The PRS adds a layer of genetic information, refining risk predictions and allowing for more personalized healthcare strategies.
Challenges and considerations
Despite the potential, the implementation of PRSs in clinical settings is not without challenges. One significant hurdle is the need for large, diverse datasets to ensure the accuracy and generalizability of PRSs across different populations. The most current PRS models are based on data from people of European descent, which may limit their applicability to other ethnic groups.
Dr. Ortega emphasizes the importance of inclusivity in genetic research by stating: "My grandmother died of asthma, and that should not have happened. She was Puerto Rican like me, and Puerto Ricans have the highest severity and frequency of asthma of any ethnic group in the world. They also represent less than 1% of people in genetic studies. So I've made it a life mission to develop cures and diagnostics for people like my grandma, and for all people."
Additionally, ethical considerations must be addressed. The use of genetic information raises concerns about privacy, potential discrimination and the psychological impact of knowing one's genetic risk. It is crucial to establish ethical guidelines and provide genetic counseling to help people understand and cope with their risk scores.
The future of PRS is bright, with ongoing research aimed at improving the accuracy and use of these scores. Advances in genome-wide association studies (GWAS) and machine learning algorithms are expected to enhance the predictive power of PRS. Furthermore, integrating PRS with other omics data, such as proteomics and metabolomics, could provide a more holistic view of a person's health.
As the field progresses, it is essential to continue fostering collaboration between researchers, clinicians and policymakers to ensure that the benefits of polygenic risk scores are realized equitably across all populations. By addressing current limitations and ethical challenges, polygenic risk scores — a significant advancement in genomics — have the potential to revolutionize preventive medicine and improve health outcomes on a global scale, paving the way for a new era of precision medicine and ultimately enhancing patient care and outcomes.
For more information
Refer a patient to Mayo Clinic.