Polygenic risk scores: how much do they add?

Area of Science:

• Genetics
• Cardiology
• Preventive Medicine

Background:

• Current genetic risk assessment for familial hypercholesterolemia and coronary artery disease (CAD) primarily relies on identifying monogenic mutations in known genes.
• Existing risk prediction tools for CAD often fail to fully account for polygenic susceptibility.

Purpose of the Study:

• To review recent advancements in polygenic risk scores (PRSs) for LDL cholesterol and CAD.
• To explore how PRSs can enhance current risk prediction algorithms for cardiovascular disease.

Main Methods:

• Review of current literature on polygenic risk scores (PRSs) for LDL cholesterol and CAD.
• Analysis of the potential integration of PRSs into existing cardiovascular risk prediction models.

Main Results:

• Polygenic risk scores (PRSs) can identify 10-20 times more individuals at high genetic risk compared to monogenic mutation testing.
• PRSs can modulate the risk associated with monogenic variants and identify patient subgroups likely to benefit from lipid-lowering therapies.
• PRSs offer early risk assessment from birth, predating other risk factors and clinical disease manifestations.

Conclusions:

• Polygenic risk scores (PRSs) for CAD are nearing clinical implementation, necessitating the establishment of analytical and clinical reporting standards.
• Validation of PRSs across diverse ethnicities and the integration of intervention thresholds into established risk scores are crucial.
• Comprehensive training for healthcare professionals is required for effective communication of polygenic risk to patients.