Frequency of pharmacogenomic variation and medication exposures among participants in the All of Us Research Program

Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in pharmacogenomics studies impedes clinical translation and the application of precision medicine across populations. We evaluated the frequencies of variants in 16 pharmacogenes ( ABCG2 , CACNA1S , CYP2D6 , CYP2C Cluster , CYP2C19 , CYP2C9 , CYP3A5 , CYP4F2 , DPYD , G6PD , NUDT15 , RYR1 , SLCO1B1 , TPMT , UGT1A1 , and VKORC1 ) and predicted phenotypes and medication exposures using whole-genome sequencing and electronic health record data from nearly 100,000 All of Us Research Program participants. We report that 100% of participants carried at least one pharmacogenomic variant and nearly all (99.5%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with 24.4% of participants having both an actionable phenotype for these pharmacogenes and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we report thousands of previously unrecognized pharmacogene variants and hundreds of alleles and predicted phenotypes that deviate from known frequencies across populations or were previously unreported, especially in the Americas and African ancestry groups.

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Publication Details

Journal
Science Translational Medicine
Published
2026-11-11
DOI
https://doi.org/10.1126/scitranslmed.adt8040
Citations
18
Primary Topic
Pharmacogenetics and Drug Metabolism
Type
article
Field-Weighted Citation Impact
27.03

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article

Frequency of pharmacogenomic variation and medication exposures among participants in the All of Us Research Program

Sean R. McGee, Beverly Wilson Holmes, Vivian Colón‐López, Jason H. Karnes et al.
18 citations
Science Translational Medicine
Pharmacogenetics and Drug Metabolism
27.03
article

Frequency of pharmacogenomic variation and medication exposures among participants in the All of Us Research Program

Sean R. McGee, Beverly Wilson Holmes, Vivian Colón‐López, Jason H. Karnes, Librada Callender, Priscilla Igho–Pemu, Eric Boerwinkle, Suchitra Chandrasekaran, Katie Baca-Motes, Marsha M. Wheeler, Maria Argos, Sara E. Kalla, Karynne Patterson, Gretchen Funk, Qiaoyan Wang, Lourdes Guerrios‐Rivera, Ingrid Bonilla-Mercado, Joyce Ho, Aparna Radhakrishnan, Andrea H. Ramirez, Joshua D. Smith, Gail Pairitz Jarvik, Richard A. Gibbs, Scott Joseph Hebbring, Kimberly Walker, Eric Venner, Joshua C. Denny, Philip E. Empey, Janeth I. Sanchez, Kathy DeerInWater, Anjene Musick Addington, Gillian Bartlett‐Esquilant, Ali G. Gharavi, David Glazer, Zeno Frano, Yuri Fresko, Liliana Lombardi Desa, Andrew Haddad, Habib Ahsan, Karl Cooper, Robert Hiatt, Kim Enard, Mark Edmunds, Roberta Carlin, Divya Kalra, Brian Ahmedani, Elizabeth Cohn, Kathleen Polkowski, Melissa Basford, Michael Garrett, Alexander Charney, Jessica Burke, Mine Cicek, Richard Grucza, Martha Daviglus, Laura Horne, Jessica Isom, Mark Begale, Cheryl Clark, Elizabeth Burnside, Marc Goodman, Evan Eichler, Stacey Gabriel, Laura Bartlett, Olveen Carrasquillo, Alejandro Comellas, George Hripcsak, Sandra Halverson, Brad Bryan, Elizabeth Culler, Milton Eder, Becky Fein, Linda Cottler, Errol Crook, Marie Gantz, Dorothy Farrar-Edwards, Rachel Everhart, Kim Doheny, Dmitry Abramov, Jacob Ditsch, Matthew Breeden, Charles Drum, Allen Greiner, Leslie Eiland, Rosario Isasi, Amaryllis Silva Boschetti, Hoda Anton-Culver, Paul Harris, Adolph Falcon, Alexander Borowsky, Eileen Handberg, Brisa Aschebook-Kilfoy, Leland Baskin, Lisa Cadmus-Bertram, William R. Hogan, Dave W. Arnold, Aditi Gupta, Philip Greenland, Catherine Balthazar
article en
18 citations

Abstract

Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in pharmacogenomics studies impedes clinical translation and the application of precision medicine across populations. We evaluated the frequencies of variants in 16 pharmacogenes ( ABCG2 , CACNA1S , CYP2D6 , CYP2C Cluster , CYP2C19 , CYP2C9 , CYP3A5 , CYP4F2 , DPYD , G6PD , NUDT15 , RYR1 , SLCO1B1 , TPMT , UGT1A1 , and VKORC1 ) and predicted phenotypes and medication exposures using whole-genome sequencing and electronic health record data from nearly 100,000 All of Us Research Program participants. We report that 100% of participants carried at least one pharmacogenomic variant and nearly all (99.5%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with 24.4% of participants having both an actionable phenotype for these pharmacogenes and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we report thousands of previously unrecognized pharmacogene variants and hundreds of alleles and predicted phenotypes that deviate from known frequencies across populations or were previously unreported, especially in the Americas and African ancestry groups.

Science Translational MedicineVol. 18(875)
National Institutes of Health (US), University of Arizona (US), University of Pittsburgh (US), Baylor College of Medicine (US), University of Washington (US), Office of the Director (US)
National Institutes of Health, National Heart, Lung, and Blood Institute
Good health and well-being
Openalex Percentile: Top 0%
Pharmacogenetics and Drug Metabolism
27.03
DOIOpen Access PDFOpenAlex
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