Recent research has suggested that polygenic risk scores (PRS) may have a role in identifying indivi
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The Role of Polygenic Risk Scores (PRS) in Disease Prediction and Clinical Utility
Introduction to Polygenic Risk Scores (PRS)
Polygenic risk scores (PRS) are emerging as a significant tool in the field of genetic research and personalized medicine. PRS aggregate the effects of numerous genetic variants across the genome to estimate an individual's genetic predisposition to various diseases1 4. These scores are derived from genome-wide association studies (GWAS) and have shown potential in predicting the risk of common complex disorders1 4.
PRS in Disease Prediction
Cancer Risk Prediction
Recent studies have demonstrated the utility of PRS in identifying individuals at high risk for several common cancers. For instance, individuals in the highest 5% of PRS for cancers such as prostate, breast, pancreas, colorectal, and ovarian cancer have a two- to threefold increased risk compared to those at average risk3. This suggests that PRS can be a valuable tool in cancer risk stratification and early detection efforts3.
Cardiometabolic Diseases
PRS have also shown promise in predicting cardiometabolic diseases. For example, PRS for coronary artery disease, hypertension, and cerebrovascular disease have been found to be as predictive, if not more so, than traditional risk factors8. Integrating PRS with clinical risk models, such as the Framingham Risk Score, has been shown to improve predictive accuracy, highlighting the potential of PRS in enhancing current risk prediction frameworks8.
Diabetes Risk in Diverse Populations
The efficacy of PRS in predicting type 2 diabetes (T2D) has been validated in diverse populations. Ancestry-specific PRS for Asian Indians, for instance, have shown significantly improved predictive power compared to European-derived PRS2. This underscores the importance of developing and validating PRS in diverse ethnic groups to ensure their broad applicability and accuracy2.
Clinical Utility and Implementation Challenges
Potential Clinical Applications
PRS could be integrated into clinical practice in several ways. They may assist in early diagnosis, inform treatment choices, and help stratify individuals for preventive interventions1 4 7. For example, in psychiatry, PRS could aid in determining follow-up options for individuals at clinical risk of future mental health disorders10. Additionally, PRS could contribute to treatment decisions by predicting adverse physical health outcomes or responses to treatment10.
Limitations and Considerations
Despite their potential, several challenges must be addressed before PRS can be widely implemented in clinical settings. One major limitation is the current low discriminative ability of PRS in the general population, which limits their standalone clinical utility1 4. Moreover, the majority of PRS research has been conducted in populations of European ancestry, raising concerns about the transferability and accuracy of PRS in other ethnic groups1 2 8.
Ethical and Practical Considerations
The use of PRS in clinical practice also raises ethical issues, such as the potential for genetic discrimination and the need for informed consent. It is crucial to set realistic expectations about what PRS can and cannot deliver and to ensure that their use is guided by robust ethical standards4 10.
Conclusion
Polygenic risk scores hold significant promise for enhancing disease prediction and personalized medicine. While they have shown potential in predicting the risk of various diseases, including cancers, cardiometabolic diseases, and diabetes, several challenges remain. Addressing issues related to predictive accuracy, population diversity, and ethical considerations will be crucial for the successful integration of PRS into clinical practice. As research progresses, PRS could become a valuable tool in the arsenal of precision medicine, aiding in early diagnosis, risk stratification, and personalized treatment strategies.
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Most relevant research papers on this topic
Polygenic risk scores: from research tools to clinical instruments
Polygenic risk scores show promise in research but need further development for clinical implementation, particularly in early stages of diseases and for non-European ancestry.
Literature Review
Rigorous Journal
Highly Cited1477-P: Improved Diabetes Risk Prediction Using Ancestry-Specific Polygenic Score—Results from the Asian Indian Diabetic Heart Study/Sikh Diabetes Study
Ancestry-specific polygenic risk scores (PRSI) are more effective than European-derived ones in predicting type 2 diabetes risk in Asian Indians.
Meta-AnalysisEvaluating the Utility of Polygenic Risk Scores in Identifying High-Risk Individuals for Eight Common Cancers
Polygenic risk scores (PRS) effectively identify a large proportion of the general population at elevated cancer risk, supporting their potential clinical utility for personalized cancer risk prediction.
Observational StudyRigorous JournalHighly CitedFrom Basic Science to Clinical Application of Polygenic Risk Scores: A Primer.
Polygenic risk scores (PRS) can predict genetic susceptibility to diseases, but their utility in clinical medicine should be evaluated within realistic expectations and ethical guidelines.
Literature ReviewHighly CitedTutorial: a guide to performing polygenic risk score analyses
This paper provides detailed guidelines for performing and interpreting polygenic risk score analyses, highlighting common misconceptions and offering an introductory online tutorial for users.
Literature ReviewHighly CitedTutorial: a guide to performing polygenic risk score analyses
This tutorial provides guidelines for performing polygenic risk score analyses, addressing common misconceptions and future challenges in personalised medicine.
Highly CitedTowards clinical utility of polygenic risk scores.
Polygenic risk scores (PRS) show promise in disease risk prediction for multiple common diseases, but further studies are needed to address implementation, ancestry bias, and transferability issues.
Literature ReviewRigorous JournalHighly CitedCurrent State and Future of Polygenic Risk Scores in Cardiometabolic Disease: A Scoping Review
Polygenic risk scores (PRSs) show strong clinical utility in cardiometabolic diseases, with predictive performance similar to or superior to traditional risk factors, but their transferability across different ancestral groups is limited.
Systematic ReviewImproving reporting standards for polygenic scores in risk prediction studies
The PRS-RS, a 33-item reporting framework, improves the translation of polygenic risk scores into clinical care by defining minimal information needed for interpretation and evaluation.
Rigorous JournalHighly CitedCould Polygenic Risk Scores Be Useful in Psychiatry?: A Review.
Polygenic risk scores show promise in aiding clinical decision-making in psychiatry when combined with other risk factors, but their utility and ethical issues require further evaluation.
Literature ReviewHighly Cited