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; Harsha Vardhan 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

doi:10.1016/j.gim.2022.01.022

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. CaraballoKonstantinos N. Lazaridis, Eric Venner, Xiang Qin, Jianhong Hu, Christie L. Kovar, Viktoriya Korchina, Kimberly Walker, Harsha Vardhan 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Journal	Genetics in Medicine
DOIs	https://doi.org/10.1016/j.gim.2022.01.022
State	Accepted/In press - 2022

Keywords

Clinical translation
Implementation
Individualized medicine
Pharmacogenomics
Pre-emptive clinical DNA sequencing

ASJC Scopus subject areas

Genetics(clinical)

Access to Document

10.1016/j.gim.2022.01.022

Cite this

Wang, L., Scherer, S. E., Bielinski, S. J., Muzny, D. M., Jones, L. A., Black, J. L., Moyer, A. M., Giri, J., Sharp, R. R., Matey, E. T., Wright, J. A., Oyen, L. J., Nicholson, W. T., Wiepert, M., Sullard, T., Curry, T. B., Rohrer Vitek, C. R., McAllister, T. M., St. Sauver, J. L., ... Weinshilboum, R. M. (Accepted/In press). Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study. Genetics in Medicine. https://doi.org/10.1016/j.gim.2022.01.022

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, Harsha Vardhan; 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.

In: Genetics in Medicine, 2022.

Research output: Contribution to journal › Article › peer-review

Wang, L, Scherer, SE, Bielinski, SJ, Muzny, DM, Jones, LA, Black, JL, Moyer, AM, Giri, J, Sharp, RR, Matey, ET, Wright, JA, Oyen, LJ, Nicholson, WT, Wiepert, M, Sullard, T, Curry, TB, Rohrer Vitek, CR, McAllister, TM, St. Sauver, JL , Caraballo, PJ , Lazaridis, KN, Venner, E, Qin, X, Hu, J, Kovar, CL, Korchina, V, Walker, K, Doddapaneni, HV, Wu, TJ, Raj, R, Denson, S, Liu, W, Chandanavelli, G, Zhang, L, Wang, Q, Kalra, D, Karow, MB, Harris, KJ, Sicotte, H, Peterson, SE, Barthel, AE, Moore, BE, Skierka, JM, Kluge, ML, Kotzer, KE, Kloke, K, Vander Pol, JM, Marker, H, Sutton, JA, Kekic, A, Ebenhoh, A, Bierle, DM, Schuh, MJ, Grilli, C, Erickson, S, Umbreit, A, Ward, L, Crosby, S, Nelson, EA, Levey, S, Elliott, M, Peters, SG, Pereira, N , Frye, M, Shamoun, F, Goetz, MP , Kullo, IJ, Wermers, R, Anderson, JA, Formea, CM, El Melik, RM, Zeuli, JD, Herges, JR, Krieger, CA, Hoel, RW, Taraba, JL, St. Thomas, SR, Absah, I, Bernard, ME, Fink, SR, Gossard, A, Grubbs, PL, Jacobson, TM, Takahashi, P, Zehe, SC, Buckles, S, Bumgardner, M, Gallagher, C, Fee-Schroeder, K, Nicholas, NR, Powers, ML, Ragab, AK, Richardson, DM, Stai, A, Wilson, J, Pacyna, JE, Olson, JE, Sutton, EJ, Beck, AT, Horrow, C, Kalari, KR , Larson, NB , Liu, H, Wang, L, Lopes, GS, Borah, BJ , Freimuth, RR, Zhu, Y, Jacobson, DJ, Hathcock, MA, Armasu, SM, McGree, ME, Jiang, R, Koep, TH, Ross, JL, Hilden, MG, Bosse, K, Ramey, B, Searcy, I, Boerwinkle, E, Gibbs, RA & Weinshilboum, RM 2022, 'Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study', Genetics in Medicine. https://doi.org/10.1016/j.gim.2022.01.022

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, Harsha Vardhan ; 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. / Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center : The Mayo-Baylor RIGHT 10K Study. In: Genetics in Medicine. 2022.

@article{f2cf24917d32424d8ad51c5e3592c144,

title = "Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study",

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.",

keywords = "Clinical translation, Implementation, Individualized medicine, Pharmacogenomics, Pre-emptive clinical DNA sequencing",

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

note = "Funding Information: This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery; Mayo Clinic Pharmacy Services; the Augeo Foundation; the; Satter Foundation; Bernard E. and Edith B. Waterman; William G. Little; Roche Diagnostics Corporation; National Science Foundation 2041339; National Institutes of Health grants U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project), and U01 HG06379 and U01 HG06379 Supplements (The Electronic Medical Record and Genomics [eMERGE] Network). The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. We wish to thank Duan Liu (Mayo Clinic) for his assistance with the preparation of this manuscript, and Michele J. Swift (Mayo Clinic) for her administrative assistance. Compensation was not received for their contributions. Conceptualization: Lie.W. S.J.B. R.M.W. R.A.G. E.B. S.E.S; Data Curation: E.V. X.Q. J.M.V.P. C.M.F. A.S.; Formal Analysis: Lie.W. S.J.B. D.M.M. S.E.S. X.Q. K.W. T.-J.W. Q.W. D.K. J.L.BIII. A.M.M. M.B.K. K.J.H. H.S. S.E.P. J.E.O. K.R.K. N.B.L. H.L. Liw.W. G.S.L. B.J.B. R.R.F. Y.Z. D.J.J. M.A.H. S.M.A. M.E.M. R.J.; Funding Acquisition: R.M.W. R.A.G.; Investigation: S.J.B. R.M.W. D.M.M. S.E.S. J.L.BIII. A.M.M. T.B.C.; Methodology: Lie.W. S.J.B. M.W. J.L.S. R.M.W. E.B. D.M.M. S.E.S. E.V. X.Q. J.H. C.L.K. K.W. J.L.BIII. A.M.M. A.E.B. B.E.M. J.M.S. M.L.K. K.E.K. K.K. W.T.N. J.G. H.M. P.J.C. A.K. A.E. D.B. M.J.S. Ch.G. S.E. A.U. Le.W. S.C. E.A.N. S.L. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. K.N.L. R.W. J.A.A. E.T.M. J.A.W. C.M.F. R.M.E.M, J.D.Z. J.R.H. C.A.K. R.W.H. J.L.T. T.B.C. T.M.M. C.R.R.V. S.R.S.T, I.A. M.E.B. S.R.F. A.G. P.L.G. T.M.J. P.T. M.B. K.F.-S. N.R.N. A.K.R. D.M.R. J.W. R.R.S.; Project Administration: Lie.W. S.J.B. L.A.J. M.W. T.S. J.L.S. R.M.W. R.A.G. E.B. D.M.M. S.E.S. C.L.K. V.K. J.L.BIII. A.M.M. W.T.N. J.G. P.J.C. S.E. K.N.L. L.J.O. E.T.M. J.A.W. T.B.C. T.M.M. C.R.R.V. R.R.S.; Resources: S.J.B. H.D. R.R. S.D. W.L. G.C. L.Z. A.E.B. J.M.V.P. S.C.Z. S.B. Co.G. M.L.P. J.E.P. J.E.O. E.J.S. A.T.B. C.H.; Software: M.W. E.V. X.Q. K.W. T.-J.W. J.L.BIII. K.J.H. H.S. S.E.P. J.M.V.P. J.S. A.S. T.H.K. J.L.R. M.G.H. K.B. B.R. I.S.; Supervision: Lie.W. S.J.B. L.A.J. M.W. T.S. J.L.S. R.M.W. R.A.G. E.B. D.M.M. S.E.S. E.V. J.H. K.W. H.D. R.R. W.L. J.L.BIII. A.E.B. K.K. W.T.N. H.M. P.J.C. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. K.N.L. R.W. L.J.O. T.B.C. T.M.M. C.R.R.V. I.A. M.E.B. R.R.S. N.B.L.; Validation: D.M.M. S.E.S. E.V. X.Q. J.H. C.L.K. V.K. K.W. T.-J.W. R.R. S.D. W.L. G.C. L.Z. Q.W. D.K. J.L.BIII. M.B.K.; Writing-original draft: Lie.W. S.J.B. R.M.W. R.A.G. S.E.S. E.V. X.Q. J.H. V.K.; Writing-review and editing: Lie.W. S.E.S. S.J.B. D.M.M. L.A.J. J.L.BIII. A.M.M. J.G. R.R.S. E.T.M. J.A.W. L.J.O. W.T.N. M.W. T.S. T.B.C. C.R.R.V. T.M.M. J.L.S.S. P.J.C. K.N.L. E.V. X.Q. J.H. C.L.K. V.K. K.W. H.D. T.-J.W. R.R. S.D. W.L. G.C. L.Z. Q.W. D.K. M.B.K. K.J.H. H.S. S.E.P. A.E.B. B.E.M. J.M.S. M.L.K. K.E.K. K.K. J.M.V.P. H.M. J.A.S. A.K. A.E. D.M.B. M.J.S. Ch.G. S.E. A.U. Le.W. S.C. E.A.N. S.L. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. R.W. J.A.A. C.M.F. R.M.E.M. J.D.Z. J.R.H. C.A.K. R.W.H. J.L.T. S.R.S.T. I.A. M.E.B. S.R.F. A.G. P.L.G. T.M.J. P.T. S.C.Z. S.B. M.B. Co.G. K.F.-S. N.R.N. M.L.P. A.K.R. D.M.R. A.S. J.W. J.E.P. J.E.O. E.J.S. A.T.B. C.H. K.R.K. N.B.L. H.L. Liw. W. G.S.L. B.J.B. R.R.F. Y.Z. D.J.J. M.A.H. S.M.A. M.E.M. R.J. T.H.K. J.L.R. M.H. K.B. B.R. I.S. E.B. R.A.G. R.M.W. All participants in this study were recruited from the Mayo Clinic Biobank and informed consent was obtained under Mayo Clinic Institutional Review Board approval. Participants agreed to the use of their stored Biobank samples for clinical pharmacogenomic testing, deposit of pharmacogenomic results into their electronic health record for clinical use, and use of de-identified pharmacogenomic data for research. For more information on both the Biobank (https://www.mayo.edu/research/centers-programs/mayo-clinic-biobank/about/governance-oversight) and the RIGHT cohort, please see Bielinski et al.15 Funding Information: This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery; Mayo Clinic Pharmacy Services; the Augeo Foundation; the; Satter Foundation; Bernard E. and Edith B. Waterman; William G. Little; Roche Diagnostics Corporation; National Science Foundation 2041339; National Institutes of Health grants U19 GM61388 ( The Pharmacogenomics Research Network ), R01 GM28157 , U01 HG005137 , R01 GM125633 , R01 AG034676 ( The Rochester Epidemiology Project ), and U01 HG06379 and U01 HG06379 Supplements ( The Electronic Medical Record and Genomics [eMERGE] Network). Publisher Copyright: {\textcopyright} 2022 American College of Medical Genetics and Genomics",

year = "2022",

doi = "10.1016/j.gim.2022.01.022",

language = "English (US)",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center

T2 - The Mayo-Baylor RIGHT 10K Study

AU - Wang, Liewei

AU - Scherer, Steven E.

AU - Bielinski, Suzette J.

AU - Muzny, Donna M.

AU - Jones, Leila A.

AU - Black, John Logan

AU - Moyer, Ann M.

AU - Giri, Jyothsna

AU - Sharp, Richard R.

AU - Matey, Eric T.

AU - Wright, Jessica A.

AU - Oyen, Lance J.

AU - Nicholson, Wayne T.

AU - Wiepert, Mathieu

AU - Sullard, Terri

AU - Curry, Timothy B.

AU - Rohrer Vitek, Carolyn R.

AU - McAllister, Tammy M.

AU - St. Sauver, Jennifer L.

AU - Caraballo, Pedro J.

AU - Lazaridis, Konstantinos N.

AU - Venner, Eric

AU - Qin, Xiang

AU - Hu, Jianhong

AU - Kovar, Christie L.

AU - Korchina, Viktoriya

AU - Walker, Kimberly

AU - Doddapaneni, Harsha Vardhan

AU - Wu, Tsung Jung

AU - Raj, Ritika

AU - Denson, Shawn

AU - Liu, Wen

AU - Chandanavelli, Gauthami

AU - Zhang, Lan

AU - Wang, Qiaoyan

AU - Kalra, Divya

AU - Karow, Mary Beth

AU - Harris, Kimberley J.

AU - Sicotte, Hugues

AU - Peterson, Sandra E.

AU - Barthel, Amy E.

AU - Moore, Brenda E.

AU - Skierka, Jennifer M.

AU - Kluge, Michelle L.

AU - Kotzer, Katrina E.

AU - Kloke, Karen

AU - Vander Pol, Jessica M.

AU - Marker, Heather

AU - Sutton, Joseph A.

AU - Kekic, Adrijana

AU - Ebenhoh, Ashley

AU - Bierle, Dennis M.

AU - Schuh, Michael J.

AU - Grilli, Christopher

AU - Erickson, Sara

AU - Umbreit, Audrey

AU - Ward, Leah

AU - Crosby, Sheena

AU - Nelson, Eric A.

AU - Levey, Sharon

AU - Elliott, Michelle

AU - Peters, Steve G.

AU - Pereira, Naveen

AU - Frye, Mark

AU - Shamoun, Fadi

AU - Goetz, Matthew P.

AU - Kullo, Iftikhar J.

AU - Wermers, Robert

AU - Anderson, Jan A.

AU - Formea, Christine M.

AU - El Melik, Razan M.

AU - Zeuli, John D.

AU - Herges, Joseph R.

AU - Krieger, Carrie A.

AU - Hoel, Robert W.

AU - Taraba, Jodi L.

AU - St. Thomas, Scott R.

AU - Absah, Imad

AU - Bernard, Matthew E.

AU - Fink, Stephanie R.

AU - Gossard, Andrea

AU - Grubbs, Pamela L.

AU - Jacobson, Therese M.

AU - Takahashi, Paul

AU - Zehe, Sharon C.

AU - Buckles, Susan

AU - Bumgardner, Michelle

AU - Gallagher, Colette

AU - Fee-Schroeder, Kelliann

AU - Nicholas, Nichole R.

AU - Powers, Melody L.

AU - Ragab, Ahmed K.

AU - Richardson, Darcy M.

AU - Stai, Anthony

AU - Wilson, Jaymi

AU - Pacyna, Joel E.

AU - Olson, Janet E.

AU - Sutton, Erica J.

AU - Beck, Annika T.

AU - Horrow, Caroline

AU - Kalari, Krishna R.

AU - Larson, Nicholas B.

AU - Liu, Hongfang

AU - Wang, Liwei

AU - Lopes, Guilherme S.

AU - Borah, Bijan J.

AU - Freimuth, Robert R.

AU - Zhu, Ye

AU - Jacobson, Debra J.

AU - Hathcock, Matthew A.

AU - Armasu, Sebastian M.

AU - McGree, Michaela E.

AU - Jiang, Ruoxiang

AU - Koep, Tyler H.

AU - Ross, Jason L.

AU - Hilden, Matthew G.

AU - Bosse, Kathleen

AU - Ramey, Bronwyn

AU - Searcy, Isabelle

AU - Boerwinkle, Eric

AU - Gibbs, Richard A.

AU - Weinshilboum, Richard M.

N1 - Funding Information: This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery; Mayo Clinic Pharmacy Services; the Augeo Foundation; the; Satter Foundation; Bernard E. and Edith B. Waterman; William G. Little; Roche Diagnostics Corporation; National Science Foundation 2041339; National Institutes of Health grants U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project), and U01 HG06379 and U01 HG06379 Supplements (The Electronic Medical Record and Genomics [eMERGE] Network). The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. We wish to thank Duan Liu (Mayo Clinic) for his assistance with the preparation of this manuscript, and Michele J. Swift (Mayo Clinic) for her administrative assistance. Compensation was not received for their contributions. Conceptualization: Lie.W. S.J.B. R.M.W. R.A.G. E.B. S.E.S; Data Curation: E.V. X.Q. J.M.V.P. C.M.F. A.S.; Formal Analysis: Lie.W. S.J.B. D.M.M. S.E.S. X.Q. K.W. T.-J.W. Q.W. D.K. J.L.BIII. A.M.M. M.B.K. K.J.H. H.S. S.E.P. J.E.O. K.R.K. N.B.L. H.L. Liw.W. G.S.L. B.J.B. R.R.F. Y.Z. D.J.J. M.A.H. S.M.A. M.E.M. R.J.; Funding Acquisition: R.M.W. R.A.G.; Investigation: S.J.B. R.M.W. D.M.M. S.E.S. J.L.BIII. A.M.M. T.B.C.; Methodology: Lie.W. S.J.B. M.W. J.L.S. R.M.W. E.B. D.M.M. S.E.S. E.V. X.Q. J.H. C.L.K. K.W. J.L.BIII. A.M.M. A.E.B. B.E.M. J.M.S. M.L.K. K.E.K. K.K. W.T.N. J.G. H.M. P.J.C. A.K. A.E. D.B. M.J.S. Ch.G. S.E. A.U. Le.W. S.C. E.A.N. S.L. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. K.N.L. R.W. J.A.A. E.T.M. J.A.W. C.M.F. R.M.E.M, J.D.Z. J.R.H. C.A.K. R.W.H. J.L.T. T.B.C. T.M.M. C.R.R.V. S.R.S.T, I.A. M.E.B. S.R.F. A.G. P.L.G. T.M.J. P.T. M.B. K.F.-S. N.R.N. A.K.R. D.M.R. J.W. R.R.S.; Project Administration: Lie.W. S.J.B. L.A.J. M.W. T.S. J.L.S. R.M.W. R.A.G. E.B. D.M.M. S.E.S. C.L.K. V.K. J.L.BIII. A.M.M. W.T.N. J.G. P.J.C. S.E. K.N.L. L.J.O. E.T.M. J.A.W. T.B.C. T.M.M. C.R.R.V. R.R.S.; Resources: S.J.B. H.D. R.R. S.D. W.L. G.C. L.Z. A.E.B. J.M.V.P. S.C.Z. S.B. Co.G. M.L.P. J.E.P. J.E.O. E.J.S. A.T.B. C.H.; Software: M.W. E.V. X.Q. K.W. T.-J.W. J.L.BIII. K.J.H. H.S. S.E.P. J.M.V.P. J.S. A.S. T.H.K. J.L.R. M.G.H. K.B. B.R. I.S.; Supervision: Lie.W. S.J.B. L.A.J. M.W. T.S. J.L.S. R.M.W. R.A.G. E.B. D.M.M. S.E.S. E.V. J.H. K.W. H.D. R.R. W.L. J.L.BIII. A.E.B. K.K. W.T.N. H.M. P.J.C. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. K.N.L. R.W. L.J.O. T.B.C. T.M.M. C.R.R.V. I.A. M.E.B. R.R.S. N.B.L.; Validation: D.M.M. S.E.S. E.V. X.Q. J.H. C.L.K. V.K. K.W. T.-J.W. R.R. S.D. W.L. G.C. L.Z. Q.W. D.K. J.L.BIII. M.B.K.; Writing-original draft: Lie.W. S.J.B. R.M.W. R.A.G. S.E.S. E.V. X.Q. J.H. V.K.; Writing-review and editing: Lie.W. S.E.S. S.J.B. D.M.M. L.A.J. J.L.BIII. A.M.M. J.G. R.R.S. E.T.M. J.A.W. L.J.O. W.T.N. M.W. T.S. T.B.C. C.R.R.V. T.M.M. J.L.S.S. P.J.C. K.N.L. E.V. X.Q. J.H. C.L.K. V.K. K.W. H.D. T.-J.W. R.R. S.D. W.L. G.C. L.Z. Q.W. D.K. M.B.K. K.J.H. H.S. S.E.P. A.E.B. B.E.M. J.M.S. M.L.K. K.E.K. K.K. J.M.V.P. H.M. J.A.S. A.K. A.E. D.M.B. M.J.S. Ch.G. S.E. A.U. Le.W. S.C. E.A.N. S.L. M.E. S.G.P. N.P. M.F. F.S. M.P.G. I.J.K. R.W. J.A.A. C.M.F. R.M.E.M. J.D.Z. J.R.H. C.A.K. R.W.H. J.L.T. S.R.S.T. I.A. M.E.B. S.R.F. A.G. P.L.G. T.M.J. P.T. S.C.Z. S.B. M.B. Co.G. K.F.-S. N.R.N. M.L.P. A.K.R. D.M.R. A.S. J.W. J.E.P. J.E.O. E.J.S. A.T.B. C.H. K.R.K. N.B.L. H.L. Liw. W. G.S.L. B.J.B. R.R.F. Y.Z. D.J.J. M.A.H. S.M.A. M.E.M. R.J. T.H.K. J.L.R. M.H. K.B. B.R. I.S. E.B. R.A.G. R.M.W. All participants in this study were recruited from the Mayo Clinic Biobank and informed consent was obtained under Mayo Clinic Institutional Review Board approval. Participants agreed to the use of their stored Biobank samples for clinical pharmacogenomic testing, deposit of pharmacogenomic results into their electronic health record for clinical use, and use of de-identified pharmacogenomic data for research. For more information on both the Biobank (https://www.mayo.edu/research/centers-programs/mayo-clinic-biobank/about/governance-oversight) and the RIGHT cohort, please see Bielinski et al.15 Funding Information: This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery; Mayo Clinic Pharmacy Services; the Augeo Foundation; the; Satter Foundation; Bernard E. and Edith B. Waterman; William G. Little; Roche Diagnostics Corporation; National Science Foundation 2041339; National Institutes of Health grants U19 GM61388 ( The Pharmacogenomics Research Network ), R01 GM28157 , U01 HG005137 , R01 GM125633 , R01 AG034676 ( The Rochester Epidemiology Project ), and U01 HG06379 and U01 HG06379 Supplements ( The Electronic Medical Record and Genomics [eMERGE] Network). Publisher Copyright: © 2022 American College of Medical Genetics and Genomics

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Clinical translation

KW - Implementation

KW - Individualized medicine

KW - Pharmacogenomics

KW - Pre-emptive clinical DNA sequencing

UR - http://www.scopus.com/inward/record.url?scp=85127847512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127847512&partnerID=8YFLogxK

U2 - 10.1016/j.gim.2022.01.022

DO - 10.1016/j.gim.2022.01.022

M3 - Article

C2 - 35331649

AN - SCOPUS:85127847512

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

ER -

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

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