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Planning and Executing a Genome Wide Association Study (GWAS)

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Molecular Endocrinology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 590))

Abstract

In recent years, genome-wide association approaches have proven a powerful and successful strategy to identify genetic contributors to complex traits, including a number of endocrine disorders. Their success has meant that genome wide association studies (GWAS) are fast becoming the default study design for discovery of new genetic variants that influence a clinical trait or phenotype. This chapter focuses on a number of key elements that require consideration for the successful conduct of a GWAS. Although many of the considerations are common to any genetic study, the greater cost, extreme multiple testing, and greater openness to data sharing require specific awareness and planning by investigators. In the section on designing a GWAS, we reflect on ethical considerations, study design, selection of phenotype/s, power considerations, sample tracking and storage issues, and genotyping product selection. During execution, important considerations include DNA quantity and preparation, genotyping methods, quality control checks of genotype data, in silico genotyping (imputation), tests of association, and replication of association signals. Although the field of human genetics is rapidly evolving, recent experiences can help guide an investigator in making practical and methodological choices that will eventually determine the overall quality of GWAS results. Given the investment to recruit patient populations or cohorts that are powered for a GWAS, and the still substantial costs associated with genotyping, it is helpful to be aware of these aspects to maximize the likelihood of success, especially where there is an opportunity for implementing them prospectively.

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Acknowledgments

We wish to thank Andrew Singleton, Ph.D., National Institute on Aging, Kathleen H. Day, University of Virginia and Fang-Chi Hsu, Ph.D., Wake Forest University School of Medicine, for helpful discussion and comments.

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Authors and Affiliations

  1. Departments of Medicine and Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

    Michèle M. Sale, Josyf C. Mychaleckyj & Wei-Min Chen

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  1. Michèle M. Sale
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  2. Josyf C. Mychaleckyj
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  3. Wei-Min Chen
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Editor information

Editors and Affiliations

  1. College of Medicine, University of Kentucky, Rose Street 800, Lexington, 40536-0298, U.S.A.

    Ok-Kyong Park-Sarge

  2. Dept. Obstetrics & Gynecology, University of Kentucky, Rose Street 800, Lexington, 40536-0293, U.S.A.

    Thomas E. Curry

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Sale, M.M., Mychaleckyj, J.C., Chen, WM. (2009). Planning and Executing a Genome Wide Association Study (GWAS). In: Park-Sarge, OK., Curry, T. (eds) Molecular Endocrinology. Methods in Molecular Biology, vol 590. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-378-7_25

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  • DOI: https://doi.org/10.1007/978-1-60327-378-7_25

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-377-0

  • Online ISBN: 978-1-60327-378-7

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