The Merits of Testing Hardy-Weinberg Equilibrium in the Analysis of Unmatched Case-Control Data: A Cautionary Note

Authors

  • Guang Yong Zou,

    Corresponding author
    1. Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada and Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada
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  • Allan Donner

    1. Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada and Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada
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*Corresponding author: Guang Yong Zou, Robarts Clinical Trials Robarts Research Institute, London, Ontario, Canada N6A 5K8 Tel: 519-663-3400 Ext 34092 Fax: 519-663-3807 Email: gzou@robarts.ca

Summary

Testing for departures from the assumption of Hardy-Weinberg equilibrium (HWE) has been widely recommended as a preliminary step in the analysis of genetic case-control studies. Some authors suggest using a two-stage procedure in which gene/disease associations are ultimately evaluated using either the Pearson chi-square procedure or the Cochran-Armitage test for trend. Other authors go further and encourage investigators to discard data that are in violation of HWE, essentially using the test as a tool for identifying genotyping errors. In this paper we show that 1) testing for HWE should not be used as a tool to identify genotyping errors; and 2) it is not necessary, and possibly even harmful, to test the HWE assumption before testing for association between alleles and disease. Instead one should inherently account for deviations from HWE with an adjusted chi-square test statistic, a procedure which in the present context is identical to the trend test. Examples from previous reports are used to illustrate the methodology.

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