Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network

W. S. Bush; D. R. Crosslin; A. Owusu-Obeng; J. Wallace; B. Almoguera; M. A. Basford; S. J. Bielinski; D. S. Carrell; J. J. Connolly; D. Crawford; K. F. Doheny; C. J. Gallego; A. S. Gordon; B. Keating; J. Kirby; T. Kitchner; S. Manzi; A. R. Mejia; V. Pan; C. L. Perry; J. F. Peterson; C. A. Prows; J. Ralston; S. A. Scott; A. Scrol; M. Smith; S. C. Stallings; T. Veldhuizen; W. Wolf; S. Volpi; K. Wiley; R. Li; T. Manolio; E. Bottinger; M. H. Brilliant; D. Carey; R. L. Chisholm; C. G. Chute; J. L. Haines; H. Hakonarson; J. B. Harley; I. A. Holm; I. J. Kullo; G. P. Jarvik; E. B. Larson; C. A. McCarty; M. S. Williams; J. C. Denny; L. J. Rasmussen-Torvik; D. M. Roden

doi:10.1002/cpt.350

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network

W. S. Bush, D. R. Crosslin, A. Owusu-Obeng, J. Wallace, B. Almoguera, M. A. Basford, S. J. Bielinski, D. S. Carrell, J. J. Connolly, D. Crawford, K. F. Doheny, C. J. Gallego, A. S. Gordon, B. Keating, J. Kirby, T. Kitchner, S. Manzi, A. R. Mejia, V. Pan, C. L. PerryJ. F. Peterson, C. A. Prows, J. Ralston, S. A. Scott, A. Scrol, M. Smith, S. C. Stallings, T. Veldhuizen, W. Wolf, S. Volpi, K. Wiley, R. Li, T. Manolio, E. Bottinger, M. H. Brilliant, D. Carey, R. L. Chisholm, C. G. Chute, J. L. Haines, H. Hakonarson, J. B. Harley, I. A. Holm, I. J. Kullo, G. P. Jarvik, E. B. Larson, C. A. McCarty, M. S. Williams, J. C. Denny, L. J. Rasmussen-Torvik, D. M. Roden

Epidemiology

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

142 Scopus citations

Abstract

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Original language	English (US)
Pages (from-to)	160-169
Number of pages	10
Journal	Clinical pharmacology and therapeutics
DOIs	https://doi.org/10.1002/cpt.350
State	Published - Aug 1 2016

Bibliographical note

Funding Information:
The eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essential Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). The PGRNSeq dataset (eMERGE PGx), please also add U01HG004438 (CIDR) serving as a Sequencing Center. This work was also supported in part by the Mayo Clinic Center for Individualized Medicine, National Institutes of Health grants U19 GM61388 (the Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 CA138461, and R01 AG034676 (the Rochester Epidemiology Project).

Publisher Copyright:
© 2016 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Access

10.1002/cpt.350

OpenUrl availability

Full text

Cite this

Bush, W. S., Crosslin, D. R., Owusu-Obeng, A., Wallace, J., Almoguera, B., Basford, M. A., Bielinski, S. J., Carrell, D. S., Connolly, J. J., Crawford, D., Doheny, K. F., Gallego, C. J., Gordon, A. S., Keating, B., Kirby, J., Kitchner, T., Manzi, S., Mejia, A. R., Pan, V., ... Roden, D. M. (2016). Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network. Clinical pharmacology and therapeutics, 160-169. https://doi.org/10.1002/cpt.350

Bush, WS, Crosslin, DR, Owusu-Obeng, A, Wallace, J, Almoguera, B, Basford, MA, Bielinski, SJ, Carrell, DS, Connolly, JJ, Crawford, D, Doheny, KF, Gallego, CJ, Gordon, AS, Keating, B, Kirby, J, Kitchner, T, Manzi, S, Mejia, AR, Pan, V, Perry, CL, Peterson, JF, Prows, CA, Ralston, J, Scott, SA, Scrol, A, Smith, M, Stallings, SC, Veldhuizen, T, Wolf, W, Volpi, S, Wiley, K, Li, R, Manolio, T, Bottinger, E, Brilliant, MH, Carey, D, Chisholm, RL, Chute, CG, Haines, JL, Hakonarson, H, Harley, JB, Holm, IA, Kullo, IJ, Jarvik, GP, Larson, EB, McCarty, CA, Williams, MS, Denny, JC, Rasmussen-Torvik, LJ & Roden, DM 2016, 'Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network', Clinical pharmacology and therapeutics, pp. 160-169. https://doi.org/10.1002/cpt.350

@article{91ad4fea08484704a9342369e9bce638,

title = "Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network",

abstract = "Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.",

author = "Bush, {W. S.} and Crosslin, {D. R.} and A. Owusu-Obeng and J. Wallace and B. Almoguera and Basford, {M. A.} and Bielinski, {S. J.} and Carrell, {D. S.} and Connolly, {J. J.} and D. Crawford and Doheny, {K. F.} and Gallego, {C. J.} and Gordon, {A. S.} and B. Keating and J. Kirby and T. Kitchner and S. Manzi and Mejia, {A. R.} and V. Pan and Perry, {C. L.} and Peterson, {J. F.} and Prows, {C. A.} and J. Ralston and Scott, {S. A.} and A. Scrol and M. Smith and Stallings, {S. C.} and T. Veldhuizen and W. Wolf and S. Volpi and K. Wiley and R. Li and T. Manolio and E. Bottinger and Brilliant, {M. H.} and D. Carey and Chisholm, {R. L.} and Chute, {C. G.} and Haines, {J. L.} and H. Hakonarson and Harley, {J. B.} and Holm, {I. A.} and Kullo, {I. J.} and Jarvik, {G. P.} and Larson, {E. B.} and McCarty, {C. A.} and Williams, {M. S.} and Denny, {J. C.} and Rasmussen-Torvik, {L. J.} and Roden, {D. M.}",

note = "Funding Information: The eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essential Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). The PGRNSeq dataset (eMERGE PGx), please also add U01HG004438 (CIDR) serving as a Sequencing Center. This work was also supported in part by the Mayo Clinic Center for Individualized Medicine, National Institutes of Health grants U19 GM61388 (the Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 CA138461, and R01 AG034676 (the Rochester Epidemiology Project). Publisher Copyright: {\textcopyright} 2016 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.",

year = "2016",

month = aug,

day = "1",

doi = "10.1002/cpt.350",

language = "English (US)",

pages = "160--169",

journal = "Clinical pharmacology and therapeutics",

issn = "0009-9236",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genetic variation among 82 pharmacogenes

T2 - The PGRNseq data from the eMERGE network

AU - Bush, W. S.

AU - Crosslin, D. R.

AU - Owusu-Obeng, A.

AU - Wallace, J.

AU - Almoguera, B.

AU - Basford, M. A.

AU - Bielinski, S. J.

AU - Carrell, D. S.

AU - Connolly, J. J.

AU - Crawford, D.

AU - Doheny, K. F.

AU - Gallego, C. J.

AU - Gordon, A. S.

AU - Keating, B.

AU - Kirby, J.

AU - Kitchner, T.

AU - Manzi, S.

AU - Mejia, A. R.

AU - Pan, V.

AU - Perry, C. L.

AU - Peterson, J. F.

AU - Prows, C. A.

AU - Ralston, J.

AU - Scott, S. A.

AU - Scrol, A.

AU - Smith, M.

AU - Stallings, S. C.

AU - Veldhuizen, T.

AU - Wolf, W.

AU - Volpi, S.

AU - Wiley, K.

AU - Li, R.

AU - Manolio, T.

AU - Bottinger, E.

AU - Brilliant, M. H.

AU - Carey, D.

AU - Chisholm, R. L.

AU - Chute, C. G.

AU - Haines, J. L.

AU - Hakonarson, H.

AU - Harley, J. B.

AU - Holm, I. A.

AU - Kullo, I. J.

AU - Jarvik, G. P.

AU - Larson, E. B.

AU - McCarty, C. A.

AU - Williams, M. S.

AU - Denny, J. C.

AU - Rasmussen-Torvik, L. J.

AU - Roden, D. M.

N1 - Funding Information: The eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essential Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). The PGRNSeq dataset (eMERGE PGx), please also add U01HG004438 (CIDR) serving as a Sequencing Center. This work was also supported in part by the Mayo Clinic Center for Individualized Medicine, National Institutes of Health grants U19 GM61388 (the Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 CA138461, and R01 AG034676 (the Rochester Epidemiology Project). Publisher Copyright: © 2016 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

AB - Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

UR - http://www.scopus.com/inward/record.url?scp=84978129461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978129461&partnerID=8YFLogxK

U2 - 10.1002/cpt.350

DO - 10.1002/cpt.350

M3 - Article

C2 - 26857349

AN - SCOPUS:84978129461

SN - 0009-9236

SP - 160

EP - 169

JO - Clinical pharmacology and therapeutics

JF - Clinical pharmacology and therapeutics

ER -

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network

Abstract

Bibliographical note

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this