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

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

Genetics in medicine : official journal of the American College of Medical Genetics

2022  Volume 24, Issue 5, Page(s) 1062–1072

Abstract: Purpose: 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 ... ...

Abstract Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
MeSH term(s) Academic Medical Centers ; Base Sequence ; Cytochrome P-450 CYP2D6/genetics ; Genotype ; Humans ; Pharmacogenetics/methods
Chemical Substances Cytochrome P-450 CYP2D6 (EC 1.14.14.1)
Language English
Publishing date 2022-03-21
Publishing country United States
Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID 1455352-1
ISSN 1530-0366 ; 1098-3600
ISSN (online) 1530-0366
ISSN 1098-3600
DOI 10.1016/j.gim.2022.01.022
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