Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data. Academic Article uri icon

Overview

MeSH

  • Chromosome Mapping
  • Data Mining
  • Humans
  • Phenotype

MeSH Major

  • Electronic Health Records
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Medical Record Linkage
  • Polymorphism, Single Nucleotide

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

publication date

  • December 2013

has subject area

  • Chromosome Mapping
  • Data Mining
  • Electronic Health Records
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Medical Record Linkage
  • Phenotype
  • Polymorphism, Single Nucleotide

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3969265

Digital Object Identifier (DOI)

  • 10.1038/nbt.2749

PubMed ID

  • 24270849

Additional Document Info

start page

  • 1102

end page

  • 1110

volume

  • 31

number

  • 12