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


METHODS
The type 1 error rate and the power of the exact test are calculated for different sample sizes, significance 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.


CONCLUSIONS
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 occasionally exceeding the nominal level.
Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Avinguda Diagonal 647, Barcelona, Spain
Jan
J
Graffelman
Victor
V
Moreno
D000465:Algorithms; D001499:Bayes Theorem; D003110:Colonic Neoplasms / Q000235:genetics; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D005787:Gene Frequency; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods*; D060148:HapMap Project; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide
D005819:Genetic Markers