TY - JOUR
T1 - Pharmacogenomics polygenic risk score
T2 - Ready or not for prime time?
AU - Singh, Sonal
AU - Stocco, Gabriele
AU - Theken, Katherine N.
AU - Dickson, Alyson
AU - Feng, Qi Ping
AU - Karnes, Jason H.
AU - Mosley, Jonathan D.
AU - El Rouby, Nihal
N1 - Publisher Copyright:
© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2024/8
Y1 - 2024/8
N2 - Pharmacogenomic Polygenic Risk Scores (PRS) have emerged as a tool to address the polygenic nature of pharmacogenetic phenotypes, increasing the potential to predict drug response. Most pharmacogenomic PRS have been extrapolated from disease-associated variants identified by genome wide association studies (GWAS), although some have begun to utilize genetic variants from pharmacogenomic GWAS. As pharmacogenomic PRS hold the promise of enabling precision medicine, including stratified treatment approaches, it is important to assess the opportunities and challenges presented by the current data. This assessment will help determine how pharmacogenomic PRS can be advanced and transitioned into clinical use. In this review, we present a summary of recent evidence, evaluate the current status, and identify several challenges that have impeded the progress of pharmacogenomic PRS. These challenges include the reliance on extrapolations from disease genetics and limitations inherent to pharmacogenomics research such as low sample sizes, phenotyping inconsistencies, among others. We finally propose recommendations to overcome the challenges and facilitate the clinical implementation. These recommendations include standardizing methodologies for phenotyping, enhancing collaborative efforts, developing new statistical methods to capitalize on drug-specific genetic associations for PRS construction. Additional recommendations include enhancing the infrastructure that can integrate genomic data with clinical predictors, along with implementing user-friendly clinical decision tools, and patient education. Ethical and regulatory considerations should address issues related to patient privacy, informed consent and safe use of PRS. Despite these challenges, ongoing research and large-scale collaboration is likely to advance the field and realize the potential of pharmacogenomic PRS.
AB - Pharmacogenomic Polygenic Risk Scores (PRS) have emerged as a tool to address the polygenic nature of pharmacogenetic phenotypes, increasing the potential to predict drug response. Most pharmacogenomic PRS have been extrapolated from disease-associated variants identified by genome wide association studies (GWAS), although some have begun to utilize genetic variants from pharmacogenomic GWAS. As pharmacogenomic PRS hold the promise of enabling precision medicine, including stratified treatment approaches, it is important to assess the opportunities and challenges presented by the current data. This assessment will help determine how pharmacogenomic PRS can be advanced and transitioned into clinical use. In this review, we present a summary of recent evidence, evaluate the current status, and identify several challenges that have impeded the progress of pharmacogenomic PRS. These challenges include the reliance on extrapolations from disease genetics and limitations inherent to pharmacogenomics research such as low sample sizes, phenotyping inconsistencies, among others. We finally propose recommendations to overcome the challenges and facilitate the clinical implementation. These recommendations include standardizing methodologies for phenotyping, enhancing collaborative efforts, developing new statistical methods to capitalize on drug-specific genetic associations for PRS construction. Additional recommendations include enhancing the infrastructure that can integrate genomic data with clinical predictors, along with implementing user-friendly clinical decision tools, and patient education. Ethical and regulatory considerations should address issues related to patient privacy, informed consent and safe use of PRS. Despite these challenges, ongoing research and large-scale collaboration is likely to advance the field and realize the potential of pharmacogenomic PRS.
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U2 - 10.1111/cts.13893
DO - 10.1111/cts.13893
M3 - Article
C2 - 39078255
AN - SCOPUS:85200027678
SN - 1752-8054
VL - 17
JO - Clinical and Translational Science
JF - Clinical and Translational Science
IS - 8
M1 - e13893
ER -