Polygenic risk scores: from research tools to clinical instruments

Area of Science:

• Genetics
• Genomics
• Personalized Medicine

Background:

• Complex diseases exhibit polygenic architecture, influenced by multiple genetic variants.
• Polygenic risk scores (PRS) aggregate these variants to estimate an individual's disease susceptibility.
• While widely used in research, the clinical utility of PRS remains largely unproven.

Purpose of the Study:

• To review the current state and potential clinical applications of polygenic risk scores (PRS).
• To discuss the challenges and opportunities for implementing PRS in disease diagnosis and treatment.
• To explore the utility of PRS across different stages of the disease trajectory.

Main Methods:

• Review of genome-wide association studies (GWAS) findings.
• Analysis of polygenic risk score (PRS) applications in research.
• Discussion of clinical implementation challenges and potential solutions.

Main Results:

• PRS confirm associations between genetic variants and disease status in research settings.
• Current PRS show low discriminative ability in the general population for lifetime disease risk.
• Potential utility exists in specific cohorts, such as those with higher disease probability or for diagnostic assistance.

Conclusions:

• PRS show promise for estimating genetic risk but require further validation for clinical use.
• Addressing limitations, including ancestry-specific performance and risk translation, is crucial.
• Future applications may involve integrating PRS into clinical decision-making at various disease stages.