Tradeoff between no-call reduction in genotyping error rate and loss of sample size for genetic case/control association studies.
Tradeoff between no-call reduction in genotyping error rate and loss of sample size for genetic case/control association studies.
复制标题
基因分型错误率的无判别减少与遗传病例/对照关联研究的样本量损失之间的权衡。
DOI：
10.1142/9789812704856_0012
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发表时间：
2004
影响因子：
--
通讯作者：
Finch,SJ
中科院分区：
文献类型：
--
作者：
Kang,SJ;Gordon,D;Brown,AM;Ott,J;Finch,SJ
可以对单核苷酸多态性（SNP）进行基因分型，以用于病例对照设计，以使用独立性的自平方检验来测试SNP标记与疾病之间的关联。基因分型通常基于基础的连续测量，其被分类为基因型。有时使用“不调用”程序，在该程序中，不对临界观测进行分类。该程序具有降低基因型错误率和观察到的基因型预期数量的同时效果。这两个量都会影响统计量的功效。我们开发的方法来计算基因型错误率，预期数量的基因型观察到的，并作为一个功能的无调用程序的预期功率测试。我们研究统计特性的卡方检验使用无呼叫程序时，潜在的连续测量的基因型分类是一个三个组成部分的混合物的单变量正态分布下的一系列参数规格。基因型错误率随着非调用区域的增加而降低。基因分型的预期观察数量也会减少。我们的主要发现是，卡方检验的预期功效对无呼叫程序不敏感。也就是说，减少基因型错误率的好处几乎完全被减少基因型观察所造成的损失所平衡。对于要用achi平方检验分析的基因型分类的基础单变量正态混合，使用无判定程序的功效几乎没有增加（如果有的话）。
Single nucleotide polymorphisms (SNP) may be genotyped for use in case-control designs to test for association between a SNP marker and a disease using achi-squared test of independence. Genotyping is often based on underlying continuous measurements, which are classified into genotypes. A “no-call” procedure is sometimes used in which borderline observations are not classified. This procedure has the simultaneous effect of reducing the genotype error rate and the expected number of genotypes observed. Both quantities affect the power of the statistic. We develop methods for calculating the genotype error rate, the expected number of genotypes observed, and the expected power of the resulting test as a function of the no-call procedure. We examine the statistical properties of the chi-squared test using a no-call procedure when the underlying continuous measure of genotype classification is a three-component mixture of univariate normal distributions under a range of parameter specifications. The genotype error rate decreases as the no-call region is increased. The expected number of observations genotyped also decreases. Our key finding is that the expected power of the chi-squared test is not sensitive to the no-call procedure. That is, the benefits of reduced genotype error rate are almost exactly balanced by the losses due to reduced genotype observations. For an underlying univariate normal mixture of genotype classification to be analyzed with achi-squared test, there is little, if any, increase in power using a no-call procedure.