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.
authors: Case Western Reserve University, Cleveland, Ohio, USA.
authors: W S
authors: WS
authors: Bush
authors: University of Washington, Seattle, Washington, USA.
authors: D R
authors: DR
authors: Crosslin
authors: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: A
authors: A
authors: Owusu-Obeng
authors: Pennsylvania State University, University Park, Pennsylvania, USA.
authors: J
authors: J
authors: Wallace
authors: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: B
authors: B
authors: Almoguera
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: M A
authors: MA
authors: Basford
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: S J
authors: SJ
authors: Bielinski
authors: Group Health Research Institute, Seattle, Washington, USA.
authors: D S
authors: DS
authors: Carrell
authors: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: J J
authors: JJ
authors: Connolly
authors: Case Western Reserve University, Cleveland, Ohio, USA.
authors: D
authors: D
authors: Crawford
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: K F
authors: KF
authors: Doheny
authors: University of Washington, Seattle, Washington, USA.
authors: C J
authors: CJ
authors: Gallego
authors: University of Washington, Seattle, Washington, USA.
authors: A S
authors: AS
authors: Gordon
authors: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: B
authors: B
authors: Keating
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: J
authors: J
authors: Kirby
authors: Marshfield Clinic, Marshfield, Wisconsin, USA.
authors: T
authors: T
authors: Kitchner
authors: Boston Children's Hospital, Boston, Massachusetts, USA.
authors: S
authors: S
authors: Manzi
authors: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: A R
authors: AR
authors: Mejia
authors: Northwestern University Feinberg School of Medicine, Evanston, Illinois, USA.
authors: V
authors: V
authors: Pan
authors: Boston Children's Hospital, Boston, Massachusetts, USA.
authors: C L
authors: CL
authors: Perry
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: J F
authors: JF
authors: Peterson
authors: Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: C A
authors: CA
authors: Prows
authors: Group Health Research Institute, Seattle, Washington, USA.
authors: J
authors: J
authors: Ralston
authors: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: S A
authors: SA
authors: Scott
authors: Group Health Research Institute, Seattle, Washington, USA.
authors: A
authors: A
authors: Scrol
authors: Northwestern University Feinberg School of Medicine, Evanston, Illinois, USA.
authors: M
authors: M
authors: Smith
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: S C
authors: SC
authors: Stallings
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: T
authors: T
authors: Veldhuizen
authors: Boston Children's Hospital, Boston, Massachusetts, USA.
authors: W
authors: W
authors: Wolf
authors: National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: S
authors: S
authors: Volpi
authors: National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: K
authors: K
authors: Wiley
authors: National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: R
authors: R
authors: Li
authors: National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: T
authors: T
authors: Manolio
authors: Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: E
authors: E
authors: Bottinger
authors: Marshfield Clinic, Marshfield, Wisconsin, USA.
authors: M H
authors: MH
authors: Brilliant
authors: Geisinger Health System, Danville, Pennsylvania, USA.
authors: D
authors: D
authors: Carey
authors: Northwestern University Feinberg School of Medicine, Evanston, Illinois, USA.
authors: R L
authors: RL
authors: Chisholm
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: C G
authors: CG
authors: Chute
authors: Case Western Reserve University, Cleveland, Ohio, USA.
authors: J L
authors: JL
authors: Haines
authors: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: H
authors: H
authors: Hakonarson
authors: University of Cincinnati, US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
authors: J B
authors: JB
authors: Harley
authors: Department of Pediatrics, Division of Genetics and Genomics and The Manton Center for Orphan Disease Research, Boston, Massachusetts, USA.
authors: I A
authors: IA
authors: Holm
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: I J
authors: IJ
authors: Kullo
authors: University of Washington, Seattle, Washington, USA.
authors: G P
authors: GP
authors: Jarvik
authors: Group Health Research Institute, Seattle, Washington, USA.
authors: E B
authors: EB
authors: Larson
authors: Marshfield Clinic, Marshfield, Wisconsin, USA.
authors: C A
authors: CA
authors: McCarty
authors: Geisinger Health System, Danville, Pennsylvania, USA.
authors: M S
authors: MS
authors: Williams
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: J C
authors: JC
authors: Denny
authors: Northwestern University Feinberg School of Medicine, Evanston, Illinois, USA.
authors: L J
authors: LJ
authors: Rasmussen-Torvik
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors: D M
authors: DM
authors: Roden
authors: Geisinger Health System, Danville, Pennsylvania, USA.
authors: M D
authors: MD
authors: Ritchie
mesh_terms: D000368:Aged; D030541:Databases, Genetic; D057286:Electronic Health Records; D005260:Female; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D057285:Precision Medicine / Q000379:methods