Polygenic Risk Scores (PRS)
Advancing Precision Medicine with PRS
For healthcare providers and physicians seeking to delve into the intricate world of genetic risk factors, the landscape is evolving rapidly. Over the past decade, genetic testing has proven invaluable in assessing the individual risk of monogenic diseases, those conditions caused by a single genetic mutation, such as cystic fibrosis or Huntington's Disease. These tests have allowed for targeted interventions and personalized care.
Yet, the challenge remains when it comes to deciphering the risk factors associated with more common multifactorial diseases, where the interaction of hundreds to thousands of genetic variants and environmental factors plays a pivotal role. It's in this complex arena that a groundbreaking innovation emerges – Polygenic Risk Scores (PRS).
PRS represents a revolutionary leap forward in the field of precision medicine. Unlike traditional monogenic tests that focus on rare, high-impact genetic mutations responsible for single-gene disorders, PRS adopts a broader, panoramic approach. It casts a wide net across the genome, considering a multitude of common genetic variants that are distributed throughout an individual's genetic code.
In the era of precision medicine, PRS offers a promising path. It equips healthcare professionals to provide more personalized care, leading to earlier interventions and tailored health strategies. As we unravel the complexities of the human genome, PRS stands as a valuable tool in the pursuit of proactive healthcare and improved patient outcomes.
The definition of PRS
A polygenic risk score (PRS) is an individual calculation of an individual’s genetic liability to a trait or disease, computed according to their individual genetic dataset and relevant genome-wide association study (GWAS) data.
Decoding the Calculation of Polygenic Scores
Defining the impact of genetic variants on the development of specific diseases is essential. This crucial information is obtained through Genome-Wide Association Studies (GWAS). In these comprehensive studies, genetic data is compared, revealing discrepancies in the DNA of large groups, typically comprising hundreds of thousands of individuals, who either exhibit or lack a particular trait or disease. This process helps us pinpoint the significance of various genetic variations.
As the sample sizes in GWAS expand, Polygenic Risk Scores (PRSs) gain more potency. A specialized algorithm is then employed to calculate the cumulative effect of these risk-associated variants, each weighed by its individual impact on a person's DNA, resulting in a predictive score. Extensive research has indicated that PRSs exhibit greater predictive accuracy when compared to a limited number of genome-wide significant Single Nucleotide Variations (SNVs). This underscores the pivotal role that PRSs are poised to play in the realm of personalized medicine.
To validate PRSs, vast datasets from biobanks, such as the UK Biobank, are harnessed.
Unlocking the Advantages of PRS
The main benefits of PRSs include cost-effective enhancement of primary disease prevention, more refined diagnoses, slowing disease progression and recurrence, and improved precision when prescribing medicines. This broad spectrum of benefits will impact research, clinical care, clinical trial design, and public health.
The benefits
Disease risk prediction
Progression, recurrence, treatment
Disease risk prediction
In terms of disease risk prediction, the strength of the PRSs is that it identifies people at increased risk of developing a certain trait or disease who would be invisible to traditional risk models as well as optimizing those traditional models by combining them with a PRS.
Diagnostic refinement
Progression, recurrence, treatment
Disease risk prediction
It has been shown that PRSs are able to improve diagnostic accuracy which directly influences treatment options and outcomes.
Progression, recurrence, treatment
Progression, recurrence, treatment
Progression, recurrence, treatment
Recent studies have evaluated the usefulness of PRSs in regard to slowing the advancement of the disease, preventing its relapse, and reducing the requirement for using new (sometimes expensive) treatments.