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The mid p-value in exact tests for Hardy-Weinberg equilibrium

Author

Listed:
  • Graffelman Jan

    (Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Avinguda Diagonal 647, 08028 Barcelona, Spain)

  • Moreno Victor

    (Cancer Prevention Program, Catalan Institute of Oncology (ICO) Bellvitge Biomedical Research Institute (IDIBELL), Faculty of Medicine and CIBERESP, Department of Clinical Sciences, University of Barcelona (UB), Gran Via 199, 08908 L’Hospitalet del Llobregat (Barcelona), Spain)

Abstract

Objective: Exact tests for Hardy-Weinberg equilibrium are widely used in genetic association studies. We evaluate the mid p-value, unknown in the genetics literature, as an alternative for the standard p-value in the exact test.Method: The type 1 error rate and the power of the exact test are calculated for different sample sizes, sigificance levels, minor allele counts and degrees of deviation from equilibrium. Three different p-value are considered: the standard two-sided p-value, the doubled one-sided p-value and the mid p-value. Practical implications of using the mid p-value are discussed with HapMap datasets and a data set on colon cancer.Results: The mid p-value is shown to have a type 1 error rate that is always closer to the nominal level, and to have better power. Differences between the standard p-value and the mid p-value can be large for insignificant results, and are smaller for significant results. The analysis of empirical databases shows that the mid p-value uncovers more significant markers, and that the equilibrium null distribution is not tenable for both databases.Conclusion: The standard exact p-value is overly conservative, in particular for small minor allele frequencies. The mid p-value ameliorates this problem by bringing the rejection rate closer to the nominal level, at the price of ocasionally exceeding the nominal level.

Suggested Citation

  • Graffelman Jan & Moreno Victor, 2013. "The mid p-value in exact tests for Hardy-Weinberg equilibrium," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 12(4), pages 433-448, August.
  • Handle: RePEc:bpj:sagmbi:v:12:y:2013:i:4:p:433-448:n:2
    DOI: 10.1515/sagmb-2012-0039
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    References listed on IDEAS

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    1. Jon Wakefield, 2010. "Bayesian Methods for Examining Hardy–Weinberg Equilibrium," Biometrics, The International Biometric Society, vol. 66(1), pages 257-265, March.
    2. Attia John & Thakkinstian Ammarin & McElduff Patrick & Milne Elizabeth & Dawson Somer & Scott Rodney J & Klerk Nicholas de & Armstrong Bruce & Thompson John, 2010. "Detecting Genotyping Error Using Measures of Degree of Hardy-Weinberg Disequilibrium," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 9(1), pages 1-17, January.
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