Improving reporting standards for polygenic scores in risk prediction studies.

Area of Science:

• Genetics and Genomics
• Epidemiology
• Clinical Translation

Background:

• Polygenic risk scores (PRSs) aggregate genome-wide association study data for genetic disease risk estimation.
• Heterogeneity in PRS application and reporting impedes clinical translation.
• Existing reporting guidelines require updates to reflect the current state of PRS development and validation.

Purpose of the Study:

• To present the Polygenic Risk Score Reporting Standards (PRS-RS), updating the Genetic Risk Prediction Studies (GRIPS) Statement.
• To establish a comprehensive framework for interpreting and evaluating PRSs for clinical applications.
• To promote data availability, transparency, and reproducibility in PRS research.

Main Methods:

• Collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog.
• Incorporation of expert input from epidemiology, statistics, disease-specific applications, implementation, and policy.
• Development of a structured reporting framework defining minimal information for PRS interpretation and evaluation.

Main Results:

• The PRS-RS provides detailed criteria for study populations, statistical methods for PRS development and validation, and limitations.
• Emphasis on data availability and transparency, encouraging PRS deposition in the PGS Catalog.
• A structured format building on existing standards and ontologies for consistent reporting.

Conclusions:

• The PRS-RS facilitates the interpretation and evaluation of PRSs, particularly for clinical use.
• Adherence to these standards will enhance reproducibility and comparative benchmarking of PRSs.
• Implementation of the PRS-RS is expected to accelerate the translation of PRSs into clinical care and define best practices.