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Statistical Applications in Genetics and Molecular Biology

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Volume 12, Issue 4


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

Jan Graffelman
  • Corresponding author
  • Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Avinguda Diagonal 647, 08028 Barcelona, Spain
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Victor Moreno
  • 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
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Published Online: 2013-08-03 | DOI: https://doi.org/10.1515/sagmb-2012-0039


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.

Keywords: Levene-Haldane distribution; power; single nucleotide polymorphism; type I error rate


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About the article

Corresponding author: Jan Graffelman, Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Avinguda Diagonal 647, 08028 Barcelona, Spain, Phone: +34-934011739, Fax: +34-934016575

Published Online: 2013-08-03

Published in Print: 2013-08-01

Citation Information: Statistical Applications in Genetics and Molecular Biology, Volume 12, Issue 4, Pages 433–448, ISSN (Online) 1544-6115, ISSN (Print) 2194-6302, DOI: https://doi.org/10.1515/sagmb-2012-0039.

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