The need for polygenic score reporting standards in evidence-based practice: lipid genetics use case

Area of Science:

• Genetics
• Clinical Diagnostics
• Bioinformatics

Background:

• Polygenic scores (PGS) quantify genetic predisposition for heritable traits.
• Lipid PGS show potential for personalized risk assessment and clinical translation.
• Ensuring reproducibility and generalizability requires rigorous standards for PGS.

Purpose of the Study:

• To review reporting and technical standards for dyslipidemia polygenic scores (PGS).
• To evaluate PGS translation along the ACCE framework for genetic tests.
• To guide the evidence-based adoption of lipid PGS in clinical practice.

Main Methods:

• Review of applicable reporting and technical standards for dyslipidemia PGS.
• Application of the ACCE (Analytical validity, Clinical validity, Clinical utility, Ethical considerations) framework.
• Examination of recent guidance and reporting standards (e.g., ClinGen, Polygenic Score Catalog).

Main Results:

• Existing ACCE framework standards are applicable to PGS study designs.
• New PRS reporting standards define requirements for score development, validation, and translation.
• Standards address rationale, population data, model development/evaluation, and generalizability.

Conclusions:

• Lipid PGS are expected in clinical practice, necessitating clinician preparedness.
• The quality of evidence for clinical use of PGS is crucial for decision-making.
• Establishing PGS reporting standards enhances data sharing, transparency, and evidence-based practice efficiency.