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Testing Departure from Hardy-Weinberg Proportions

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Statistical Human Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1666))

Abstract

The Hardy-Weinberg principle, one of the most important principles in population genetics, was originally developed for the study of allele frequency changes in a population over generations. It is now, however, widely used in studies of human diseases to detect inbreeding, population stratification, and genotyping errors. For assessment of deviation from Hardy-Weinberg proportions in data, the most popular approaches include the asymptotic Pearson’s chi-squared goodness-of-fit test and the exact test. Pearson’s chi-squared goodness-of-fit test is simple and straightforward, but is very sensitive to a small sample size or rare allele frequency. The exact test of Hardy-Weinberg proportions is preferable in these situations. The exact test can be performed through complete enumeration of heterozygote genotypes or on the basis of the Markov chain Monte Carlo procedure. In this chapter, we describe the Hardy-Weinberg principle and the commonly used Hardy-Weinberg proportion tests and their applications, and we demonstrate how the chi-squared test and exact test of Hardy-Weinberg proportions can be performed step-by-step using the popular software programs SAS, R, and PLINK, which have been widely used in genetic association studies, along with numerical examples. We also discuss approaches for testing Hardy-Weinberg proportions in case–control study designs that are better than traditional approaches for testing Hardy-Weinberg proportions in controls only. Finally, we note that deviation from the Hardy-Weinberg proportions in affected individuals can provide evidence for an association between genetic variants and diseases.

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Authors and Affiliations

  1. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Jian Wang & Sanjay Shete

  2. Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Sanjay Shete

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  1. Jian Wang
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  2. Sanjay Shete
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Correspondence to Sanjay Shete .

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Editors and Affiliations

  1. Case Western Reserve University, Cleveland, OH, USA

    Robert C. Elston

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Wang, J., Shete, S. (2017). Testing Departure from Hardy-Weinberg Proportions. In: Elston, R. (eds) Statistical Human Genetics. Methods in Molecular Biology, vol 1666. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7274-6_6

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  • DOI: https://doi.org/10.1007/978-1-4939-7274-6_6

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