title: Enhancing the power of genetic association studies through the use of silver standard cases derived from electronic medical records.
abstract: The feasibility of using imperfectly phenotyped "silver standard" samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square test of independence using either research-quality case/control samples alone, or augmented with silver standard data. The subset of the parameter space where inclusion of silver standard samples increases statistical power is identified. A case study of dementia subjects identified from electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network, combined with subjects from two studies specifically targeting dementia, verifies these results.
authors.affiliation: Department of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. amcdavid@fhcrc.org
authors.forename: Andrew
authors.initials: A
authors.lastname: McDavid
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Newton
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.forename: Wayne
authors.initials: W
authors.lastname: McCormick
authors.forename: Noah
authors.initials: N
authors.lastname: Weston
authors.forename: Kelly
authors.initials: K
authors.lastname: Ehrlich
authors.forename: Eugene
authors.initials: E
authors.lastname: Hart
authors.forename: Robert
authors.initials: R
authors.lastname: Harrison
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.forename: Carla
authors.initials: C
authors.lastname: Rottscheit
authors.forename: Peggy
authors.initials: P
authors.lastname: Peissig
authors.forename: Elisha
authors.initials: E
authors.lastname: Stefanski
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Rebecca Lynn
authors.initials: RL
authors.lastname: Zuvich
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Kullo
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Mirel
authors.forename: Andrew
authors.initials: A
authors.lastname: Crenshaw
authors.forename: James D
authors.initials: JD
authors.lastname: Bowen
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Debby
authors.initials: D
authors.lastname: Tsuang
authors.forename: Susan
authors.initials: S
authors.lastname: McCurry
authors.forename: Linda
authors.initials: L
authors.lastname: Teri
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.forename: Chris S
authors.initials: CS
authors.lastname: Carlson
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003198:Computer Simulation; D003704:Dementia / Q000453:epidemiology / Q000235:genetics*; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers