Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

Liewei Wang, Steven E Scherer, Suzette J Bielinski, Donna M Muzny, Leila A Jones, John Logan Black, Ann M Moyer, Jyothsna Giri, Richard R Sharp, Eric T Matey, Jessica A Wright, Lance J Oyen, Wayne T Nicholson, Mathieu Wiepert, Terri Sullard, Timothy B Curry, Carolyn R Rohrer Vitek, Tammy M McAllister, Jennifer L St Sauver, Pedro J Caraballo, Konstantinos N Lazaridis, Eric Venner, Xiang Qin, Jianhong Hu, Christie L Kovar, Viktoriya Korchina, Kimberly Walker, HarshaVardhan Doddapaneni, Tsung-Jung Wu, Ritika Raj, Shawn Denson, Wen Liu, Gauthami Chandanavelli, Lan Zhang, Qiaoyan Wang, Divya Kalra, Mary Beth Karow, Kimberley J Harris, Hugues Sicotte, Sandra E Peterson, Amy E Barthel, Brenda E Moore, Jennifer M Skierka, Michelle L Kluge, Katrina E Kotzer, Karen Kloke, Jessica M Vander Pol, Heather Marker, Joseph A Sutton, Adrijana Kekic, Ashley Ebenhoh, Dennis M Bierle, Michael J Schuh, Christopher Grilli, Sara Erickson, Audrey Umbreit, Leah Ward, Sheena Crosby, Eric A Nelson, Sharon Levey, Michelle Elliott, Steve G Peters, Naveen Pereira, Mark Frye, Fadi Shamoun, Matthew P Goetz, Iftikhar J Kullo, Robert Wermers, Jan A Anderson, Christine M Formea, Razan M El Melik, John D Zeuli, Joseph R Herges, Carrie A Krieger, Robert W Hoel, Jodi L Taraba, Scott R St Thomas, Imad Absah, Matthew E Bernard, Stephanie R Fink, Andrea Gossard, Pamela L Grubbs, Therese M Jacobson, Paul Takahashi, Sharon C Zehe, Susan Buckles, Michelle Bumgardner, Colette Gallagher, Kelliann Fee-Schroeder, Nichole R Nicholas, Melody L Powers, Ahmed K Ragab, Darcy M Richardson, Anthony Stai, Jaymi Wilson, Joel E Pacyna, Janet E Olson, Erica J Sutton, Annika T Beck, Caroline Horrow, Krishna R Kalari, Nicholas B Larson, Hongfang Liu, Liwei Wang, Guilherme S Lopes, Bijan J Borah, Robert R Freimuth, Ye Zhu, Debra J Jacobson, Matthew A Hathcock, Sebastian M Armasu, Michaela E McGree, Ruoxiang Jiang, Tyler H Koep, Jason L Ross, Matthew G Hilden, Kathleen Bosse, Bronwyn Ramey, Isabelle Searcy, Eric Boerwinkle, Richard A Gibbs, Richard M Weinshilboum

Journal: Genetics in medicine : official journal of the American College of Medical Genetics 2022;24(5):1062-1072

PMID: 35331649

Abstract

[{"label":"PURPOSE","text":"The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping."},{"label":"METHODS","text":"Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record."},{"label":"RESULTS","text":"For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping."},{"label":"CONCLUSION","text":"Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources."},{"copyright":"Copyright \u00a9 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved."}]
Address: Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Clinical Pharmacology, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.; Human Genome Sequencing Center Clinical Laboratory, Baylor College of Medicine, Houston, TX.; Center for Individualized Medicine, Mayo Clinic, Rochester, MN.; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.; Biomedical Ethics Research Program, Mayo Clinic, Rochester, MN.; Department of Pharmacy, Mayo Clinic, Rochester, MN.; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN.; Department of Information Technology, Mayo Clinic, Rochester, MN.; Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN.; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.; Division of General Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX.; Department of Pharmacy, Mayo Clinic, Phoenix, AZ.; Department of Pharmacy, Mayo Clinic, Jacksonville, FL.; Supply Chain Management, Mayo Clinic, Rochester, MN.; Department of Pharmacy, Mayo Clinic Health System, Mankato, MN.; Department of Clinical Genomics, Mayo Clinic, Scottsdale, AZ.; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.; Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ.; Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN.; Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.; Department of Family Medicine, Mayo Clinic, Rochester, MN.; Division of Community Internal Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.; Department of Nursing, Mayo Clinic, Rochester, MN.; Legal Department, Mayo Clinic, Rochester, MN.; Department of Public Affairs, Mayo Clinic, Rochester, MN.; Biospecimens Accessioning and Processing Laboratory, Mayo Clinic, Rochester, MN.; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; Biomedical Ethics Research Program, Mayo Clinic, Rochester, MN.; Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.; Department of Artificial Intelligence and Informatics, Mayo Clinic, Rochester, MN.; Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN; Division of Health Care Policy and Research, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.; OneOme, LLC, Minneapolis, MN.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; Human Genome Sequencing Center Clinical Laboratory, Baylor College of Medicine, Houston, TX; School of Public Health, University of Texas Health Science Center at Houston (UTHealth), Houston, TX.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. Electronic address: [email protected].; Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Clinical Pharmacology, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN. Electronic address: [email protected].
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