title: Systematic comparison of phenome-wide association study of  electronic  medical record data and  genome-wide association study data.
abstract: Candidate gene and genome-wide association studies (GWAS) have identified genetic variants that modulate risk for human disease; many of these associations require further study to replicate the results. Here we report the first large-scale application of the phenome-wide association study (PheWAS) paradigm within electronic medical records (EMRs), an unbiased approach to replication and discovery that interrogates relationships between targeted genotypes and multiple phenotypes. We scanned for associations between 3,144 single-nucleotide polymorphisms (previously implicated by GWAS as mediators of human traits) and 1,358 EMR-derived phenotypes in 13,835 individuals of European ancestry. This PheWAS replicated 66% (51/77) of sufficiently powered prior GWAS associations and revealed 63 potentially pleiotropic associations with P < 4.6 × 10⁻⁶ (false discovery rate < 0.1); the strongest of these novel associations were replicated in an independent cohort (n = 7,406). These findings validate PheWAS as a tool to allow unbiased interrogation across multiple phenotypes in EMR-based cohorts and to enhance analysis of the genomic basis of human disease.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Lisa
authors.initials: L
authors.lastname: Bastarache
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Carroll
authors.forename: Raquel
authors.initials: R
authors.lastname: Zink
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mosley
authors.forename: Julie R
authors.initials: JR
authors.lastname: Field
authors.forename: Jill M
authors.initials: JM
authors.lastname: Pulley
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Ramirez
authors.forename: Erica
authors.initials: E
authors.lastname: Bowton
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.forename: David S
authors.initials: DS
authors.lastname: Carrell
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Peissig
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pacheco
authors.forename: Luke V
authors.initials: LV
authors.lastname: Rasmussen
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chute
authors.forename: Rex L
authors.initials: RL
authors.lastname: Chisholm
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.forename: Murray H
authors.initials: MH
authors.lastname: Brilliant
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Masys
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D057225:Data Mining / Q000379:methods; D057286:Electronic Health Records / Q000706:statistics & numerical data*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data*; D006801:Humans; D008498:Medical Record Linkage / Q000379:methods*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*