The mid p-value in exact tests for Hardy-Weinberg equilibrium
The mid p-value in exact tests for Hardy-Weinberg equilibrium
复制标题
DOI：
10.1515/sagmb-2012-0039
复制
发表时间：
2013-01-01
影响因子：
0.9
通讯作者：
Moreno, Victor
中科院分区：
文献类型：
--
作者：
Graffelman, Jan;Moreno, Victor
目的：Hardy-Weinberg平衡的精确检验在遗传关联研究中有着广泛的应用。我们评估的中间p值，未知的遗传学文献中，作为一种替代的标准p值在exact test.Method：类型1的错误率和功率的精确检验计算不同的样本量，显着性水平，次要等位基因计数和偏离平衡的程度。考虑了三种不同的p值：标准双侧p值、双单侧p值和中间p值。使用的中间p值的实际影响进行了讨论与HapMap数据集和结肠cancer.Results的数据集：中间p值被证明有一个类型1的错误率，总是更接近标称水平，并有更好的权力。对于不显著的结果，标准p值和中间p值之间的差异可能较大，对于显著的结果，差异较小。实证数据库的分析表明，中间的p值揭示了更显着的标记，和平衡零分布是不成立的两个database.Conclusion：标准的精确p值是过于保守，特别是小的次要等位基因频率。中间p值通过使拒绝率更接近名义水平来改善这个问题，但代价是偶尔超过名义水平。
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.