Journal article
The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery
Genetic epidemiology, Vol.35(5), pp.410-422
07/2011
DOI: 10.1002/gepi.20589
PMCID: PMC3116446
PMID: 21594894
Abstract
The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community. © 2011 Wiley-Liss, Inc.
Details
- Title: Subtitle
- The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery
- Creators
- S.A. Pendergrass - Vanderbilt UniversityK. Brown-Gentry - Vanderbilt UniversityS.M. Dudek - Vanderbilt UniversityE.S. Torstenson - Vanderbilt UniversityJ.L. Ambite - University of Southern CaliforniaC.L. Avery - Department of Epidemiology, University of North Carolina, Chapel Hill, North CarolinaS. Buyske - Rutgers, The State University of New JerseyC. Cai - University of Southern CaliforniaM.D. Fesinmeyer - Fred Hutch Cancer CenterC. Haiman - University of Southern CaliforniaG. Heiss - University of North Carolina at Chapel HillL.A. Hindorff - National Institutes of HealthC.-N. Hsu - University of Southern CaliforniaR.D. Jackson - The Ohio State UniversityC. Kooperberg - Fred Hutch Cancer CenterL. Le Marchand - University of Hawaiʻi at MānoaY. Lin - Fred Hutch Cancer CenterT.C. Matise - Rutgers, The State University of New JerseyL. Moreland - University of PittsburghK. Monroe - University of Southern CaliforniaA.P. Reiner - University of WashingtonR. Wallace - University of IowaL.R. Wilkens - University of Hawaiʻi at MānoaD.C. Crawford - Vanderbilt UniversityM.D. Ritchie - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.35(5), pp.410-422
- DOI
- 10.1002/gepi.20589
- PMID
- 21594894
- PMCID
- PMC3116446
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- Number of pages
- 13
- Language
- English
- Date published
- 07/2011
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364433602771
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