Tests for establishing compatibility of an observed genotype distribution with Hardy-Weinberg equilibrium in the case of a biallelic locus
Tests for establishing compatibility of an observed genotype distribution with Hardy-Weinberg equilibrium in the case of a biallelic locus
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DOI：
10.1111/j.0006-341x.2004.00219.x
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发表时间：
2004-09-01
期刊：
影响因子：
1.9
通讯作者：
Wellek, S
中科院分区：
文献类型：
--
作者：
Wellek, S
用于评估遗传平衡的经典 chi(2) 程序是为确定观察到的基因型分布与满足 Hardy-Weinberg 定律的模型的拟合缺失而不是拟合优度而定制的，对于大样本程序的精确竞争者也是如此，自 20 世纪 30 年代末以来，生物统计文献中就提出了这一点。在这篇文章中，采用统计等价检验的方法来构建问题的检验，其中实际采样的基因型分布与哈代-温伯格平衡（HWE）的近似兼容性假设起到了旨在建立的替代假设的作用。这种构建的结果很大程度上取决于距离测量的选择，该距离测量用于定义包含那些不平衡程度应被视为无关的基因型分布的无差异区域。这里提出的第一个此类度量是真实参数向量与严格 HWE 中具有相同等位基因频率的基因型分布的欧几里得距离。第二个度量基于 Stevens 首次引入当前上下文的分布的（标量）参数（1938 年，优生学年鉴 8, 377-383）。第一种方法导致无条件检验（尽管如此，可以以数字精确的方式进行），第二种方法导致精确的条件检验，对于相关的假设对来说，它显示出一致最强大的无偏性（UMPU）。两项测试均根据所获得的确切功效与严格满足 HWE 的特定替代方案类别进行比较。
The classical chi(2)-procedure for the assessment of genetic equilibrium is tailored for establishing lack rather than goodness of fit of an observed genotype distribution to a model satisfying the Hardy-Weinberg law, and the same is true for the exact competitors to the large-sample procedure, which have been proposed in the biostatistical literature since the late 1930s. In this contribution, the methodology of statistical equivalence testing is adopted for the construction of tests for problems in which the assumption of approximate compatibility of the genotype distribution actually sampled with Hardy-Weinberg equilibrium (HWE) plays the role of the alternative hypothesis one aims to establish. The result of such a construction highly depends on the choice of a measure of distance to be used for defining an indifference zone containing those genotype distributions whose degree of disequilibrium shall be considered irrelevant. The first such measure proposed here is the Euclidean distance of the true parameter vector from that of a genotype distribution with identical allele frequencies being in strict HWE. The second measure is based on the (scalar) parameter of the distribution first introduced into the present context by Stevens (1938, Annals of Eugenics 8, 377-383). The first approach leads to a nonconditional test (which nevertheless can be carried out in a numerically exact way), the second to an exact conditional test shown to be uniformly most powerful unbiased (UMPU) for the associated pair of hypotheses. Both tests are compared in terms of the exact power attained against the class of those specific alternatives under which HWE is strictly satisfied.