期刊
STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY
卷 12, 期 4, 页码 433-448出版社
WALTER DE GRUYTER GMBH
DOI: 10.1515/sagmb-2012-0039
关键词
Levene-Haldane distribution; power; single nucleotide polymorphism; type I error rate
资金
- Spanish Ministry of Education and Science [ECO2011-28875, CODA-RSS MTM2009-13272]
- Instituto de Salud Carlos III [FIS PI08/1635, FIS PI08/1359]
- CIBERESP [CB07/02/2005]
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.
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