title: Contrasting Association Results between Existing PheWAS Phenotype Definition Methods and Five Validated Electronic Phenotypes.
abstract: Phenome-Wide Association Studies (PheWAS) comprehensively investigate the association between genetic variation and a wide array of outcome traits. Electronic health record (EHR) based PheWAS uses various abstractions of International Classification of Diseases, Ninth Revision (ICD-9) codes to identify case/control status for diagnoses that are used as the phenotypic variables. However, there have not been comparisons within a PheWAS between results from high quality derived phenotypes and high-throughput but potentially inaccurate use of ICD-9 codes for case/control definition. For this study we first developed a group of high quality algorithms for five phenotypes. Next we evaluated the association of these "gold standard" phenotypes and 4,636,178 genetic variants with minor allele frequency > 0.01 and compared the results from high-throughput associations at the 3 digit, 5 digit, and PheWAS codes for defining case/control status. We found that certain diseases contained similar patient populations across phenotyping methods but had differences in PheWAS.
authors.affiliation: Center for Health Research, Danville, PA, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Leader
authors.affiliation: Biomedical and Translational Informatics Program, Danville, PA, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.affiliation: Biomedical and Translational Informatics Program, Danville, PA, USA; The Center for Systems Genomics, The Pennsylvania State University, University Park, PA USA.
authors.forename: Anurag
authors.initials: A
authors.lastname: Verma
authors.affiliation: Weis Center for Research, Geisinger Health System, Danville, PA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
authors.affiliation: Center for Health Research, Danville, PA, USA.
authors.forename: Dustin N
authors.initials: DN
authors.lastname: Hartzel
authors.affiliation: Biomedical and Translational Informatics Program, Danville, PA, USA; The Center for Systems Genomics, The Pennsylvania State University, University Park, PA USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Center for Health Research, Danville, PA, USA.
authors.forename: H Lester
authors.initials: HL
authors.lastname: Kirchner
mesh_terms: D000465:Algorithms; D057286:Electronic Health Records; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D038801:International Classification of Diseases; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide