Clinical Utility of Polygenic Risk Scores for Disease Prevention in Primary Care: A Critical Evidence Review

Background/Objectives: Polygenic risk scores (PRS) combine many genetic variants to estimate disease risk. Their clinical value depends on whether the information improves preventive decisions and patient outcomes. This critical evidence review examines selected clinical, implementation, qualitative, prediction and economic studies relevant to adult primary care. Methods: Evidence was identified through public-web searches, citation tracking and executed PubMed/MEDLINE and CENTRAL searches, then selected for its relevance to preventive care. Findings were organized by clinical decision, study design and outcome, with GRADE profiles for 14 comparisons within the assessed evidence. Results: Risk disclosure linked to a shared statin decision may increase treatment initiation and lower LDL cholesterol, although its long-term cardiovascular benefit remains very uncertain. Several information programmes showed limited short-term effects on objectively measured behaviour or weight. An integrated breast-screening programme met its prespecified advanced-cancer noninferiority margin; the contribution of PRS and an effect on biopsy burden remained uncertain. Genetic subgroup analyses address whether treatment effects vary with genetic risk, a different question from whether PRS-guided care improves outcomes. Implementation studies highlight communication, workflow and access needs, while economic models depend on uptake, treatment and cost assumptions. Conclusions: The central clinical distinction is between improved prediction, changed recommendations, care received and better health. Evidence supports selected preventive decision effects and a care-pathway approach to evaluating PRS. Broader implementation requires convincing evidence of patient-important benefit, acceptable downstream harms and equitable access.