Challenges in clinical translation of polygenic risk score analyses: A systematic review.

Abstract

The translation of polygenic risk score (PRS) analyses into clinical practice is gaining momentum; yet, it remains limited by multiple implementation barriers studied across fragmented research lines. This study aims to systematically identify, classify, and synthesize these challenges and the proposed solutions in the literature. A systematic literature review is conducted following PRISMA guidelines across PubMed, Scopus, and Web of Science, from 2020 to 2025. Included studies are classified by scientific formalism and by pertinence to PRS clinical translation topic. Data extraction is focused on challenge identification, proposed solutions and validations, with challenges aggregated into cluster categories. From 1245 initial records, 54 studies were included. We identified 8 challenge categories: heterogeneity in the reporting of PRS models, complexity in model selection, technological barriers, lack of best practices for results reporting, limited clinical guidelines and educational material, lack of clinical implementation workflows, and limitations for general applicability of PRS results. We observed varying levels of conceptual clarity and uneven research efforts in proposing solutions for the identified challenges. This review offers a structured catalog of implementation challenges and representative solutions. Findings highlight the need for covering less-addressed gaps and coordinated efforts across research domains to support the effective and responsible integration of PRS analyses into clinical care.