Principles and methods for transferring polygenic risk scores across global populations

Area of Science:

• Genetics
• Genomics
• Precision Medicine

Background:

• Polygenic risk scores (PRSs) predict genetic predisposition for complex traits and diseases.
• Current PRSs are primarily developed using data from European genetic ancestries.
• This ancestry-specific development limits PRS utility and can exacerbate health disparities in non-European populations.

Purpose of the Study:

• To identify genetic and modifiable risk factors affecting PRS transferability across diverse populations.
• To review existing methods for constructing PRSs for diverse ancestries.
• To highlight the importance of developing equitable PRSs for global health.

Main Methods:

• Literature review of factors limiting PRS transferability.
• Analysis of strengths and weaknesses of current PRS construction methodologies for diverse ancestries.

Main Results:

• Genetic and modifiable factors significantly impact PRS predictive performance across different ancestries.
• Existing PRS construction methods have limitations in ensuring equitable performance in diverse populations.
• Poor transferability of PRSs contributes to health disparities.

Conclusions:

• Ensuring PRS applicability across diverse populations is essential for advancing precision medicine.
• Innovation in PRS development is needed to promote global health equity.
• Developing PRSs that benefit all populations is a critical goal for research and clinical settings.