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Phenome-Wide Association Studies: Leveraging Comprehensive Phenotypic and Genotypic Data for Discovery

  • Genomics (SM Williams, Section Editor)
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Abstract

With the large volume of clinical and epidemiological data being collected, increasingly linked to extensive genotypic data, coupled with expanding high-performance computational resources, there are considerable opportunities for comprehensively exploring the networks of connections that exist between the phenome and the genome. These networks can be identified through Phenome-Wide Association Studies (PheWAS) where the association between a collection of genetic variants, or in some cases a particular clinical lab variable, and a wide and diverse range of phenotypes, diagnoses, traits, and/or outcomes are evaluated. This is a departure from the more familiar genome-wide association study approach, which has been used to identify single nucleotide polymorphisms associated with one outcome or a very limited phenotypic domain. In addition to highlighting novel connections between multiple phenotypes and elucidating more of the phenotype-genotype landscape, PheWAS can generate new hypotheses for further exploration, and can also be used to narrow the search space for research using comprehensive data collections. The complex results of PheWAS also have the potential for uncovering new mechanistic insights. We review here how the PheWAS approach has been used with data from epidemiological studies, clinical trials, and de-identified electronic health record data. We also review methodologies for the analyses underlying PheWAS, and emerging methods developed for evaluating the comprehensive results of PheWAS including genotype–phenotype networks. This review also highlights PheWAS as an important tool for identifying new biomarkers, elucidating the genetic architecture of complex traits, and uncovering pleiotropy. There are many directions and new methodologies for the future of PheWAS analyses, from the phenotypic data to the genetic data, and herein we also discuss some of these important future PheWAS developments.

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Disclosures

SA Pendergrass declares no conflicts of interest. MD Ritchie has received research grants from the NIH and Geisinger Health Systems.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Biomedical and Translational Informatics Program, Geisinger Health System, Danville, PA, 17822, USA

    S. A. Pendergrass & Marylyn D. Ritchie

  2. Center for Systems Genomics, The Pennsylvania State University, University Park, PA, 16802, USA

    Marylyn D. Ritchie

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  1. S. A. Pendergrass
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Correspondence to Marylyn D. Ritchie.

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This article is part of the Topical Collection on Genomics.

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Pendergrass, S.A., Ritchie, M.D. Phenome-Wide Association Studies: Leveraging Comprehensive Phenotypic and Genotypic Data for Discovery. Curr Genet Med Rep 3, 92–100 (2015). https://doi.org/10.1007/s40142-015-0067-9

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  • DOI: https://doi.org/10.1007/s40142-015-0067-9

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