Genetic Variation Among 82 Pharmacogenes: The PGRNseq Data From the eMERGE Network

被引：146

作者：

Bush, W. S. ^{[1
]}

Crosslin, D. R. ^{[2
]}

Owusu-Obeng, A. ^{[3
]}

Wallace, J. ^{[4
]}

Almoguera, B. ^{[5
]}

Basford, M. A. ^{[6
]}

Bielinski, S. J. ^{[7
]}

Carrell, D. S. ^{[8
]}

Connolly, J. J. ^{[5
]}

Crawford, D. ^{[1
]}

Doheny, K. F. ^{[9
]}

Gallego, C. J. ^{[2
]}

Gordon, A. S. ^{[2
]}

Keating, B. ^{[5
]}

Kirby, J.

Kitchner, T. ^{[10
]}

Manzi, S. ^{[11
]}

Mejia, A. R. ^{[3
]}

Pan, V.

Perry, C. L. ^{[11
]}

Peterson, J. F. ^{[6
]}

Prows, C. A. ^{[13
]}

Ralston, J. ^{[8
]}

Scott, S. A. ^{[3
]}

Scrol, A.

Smith, M.

Stallings, S. C. ^{[6
]}

Veldhuizen, T. ^{[7
]}

Wolf, W.

Volpi, S. ^{[14
]}

Wiley, K. ^{[14
]}

Li, R. ^{[14
]}

Manolio, T. ^{[14
]}

Bottinger, E. ^{[3
]}

Brilliant, M. H. ^{[10
]}

Carey, D.

Chisholm, R. L. ^{[12
]}

Chute, C. G. ^{[9
]}

Haines, J. L. ^{[1
]}

Hakonarson, H. ^{[5
]}

Harley, J. B. ^{[16
]}

Holm, I. A. ^{[17
,18
]}

Kullo, I. J. ^{[7
]}

Jarvik, G. P. ^{[2
]}

Larson, E. B. ^{[8
]}

McCarty, C. A. ^{[10
]}

Williams, M. S. ^{[15
]}

Denny, J. C. ^{[6
]}

Rasmussen-Torvik, L. J. ^{[12
]}

Roden, D. M. ^{[6
]}

机构：

[1] Case Western Reserve Univ, Cleveland, OH 44106 USA

[2] Univ Washington, Seattle, WA 98195 USA

[3] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[4] Penn State Univ, University Pk, PA 16802 USA

[5] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[6] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA

[7] Mayo Clin, Rochester, MN USA

[8] Grp Hlth Res Inst, Seattle, WA USA

[9] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[10] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA

[11] Boston Childrens Hosp, Boston, MA USA

[12] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA

[13] Childrens Hosp Med Ctr, Cincinnati, OH USA

[14] Natl Human Genome Res Inst, Bethesda, MD USA

[15] Geisinger Hlth Syst, Danville, PA USA

[16] Univ Cincinnati, US Dept Vet Affairs Med Ctr, Cincinnati, OH USA

[17] Dept Pediat, Div Genet & Genom, Boston, MA USA

[18] Manton Ctr Orphan Dis Res, Boston, MA USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2016年 / 100卷 / 02期

基金：

美国国家卫生研究院;

关键词：

ELECTRONIC MEDICAL-RECORDS; GENOME-WIDE ASSOCIATION; PERSONALIZED MEDICINE; IMPLEMENTATION CONSORTIUM; DRUG RESPONSE; VARIANTS; DEPRESSION; PROGRESS; DESIGN; UNIVERSITY;

D O I：

10.1002/cpt.350

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 similar to 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.

引用

页码：160 / 169

页数：10

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