The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping.
The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. II. Individual genotyping.
复制标题
DOI：
10.1101/gr.9.3.234
复制
发表时间：
1999-03
期刊：
影响因子：
7
通讯作者：
Jun Teng;Neil Risch
中科院分区：
文献类型：
--
作者：
Jun Teng;Neil Risch
在本文中，我们考虑基于个体基因分型的检验统计。对于没有父母的同胞，但有未受影响的同胞和受影响的同胞，我们引入了一种新的检验统计量(称为TDS)，它将受影响的同胞中的等位基因频率与从整个同胞关系中估计的父母的等位基因频率进行对比。对于没有父母的兄弟姐妹，这种测试类似于TDT，对非随机交配模式完全稳健。对于有一个受影响儿童的兄弟姐妹关系，TDS测试的效率与THS测试相当(THS测试将受影响的同胞与未受影响的同胞进行比较，并基于DNA池)。然而，随着兄弟姐妹关系中受影响同胞的数量增加，TDS测试相对于THS测试的相对效率也增加了。例如，对于有三个受影响的兄弟姐妹关系，需要的家庭减少了三分之一；对于有四个受影响的家庭，需要的家庭几乎减少了一半。因此，当兄弟姐妹关系包含多个受影响的个体时，TDS测试提供了对非随机交配的能力和稳健性的增加。
In this paper we consider test statistics based on individual genotyping. For sibships without parents, but with unaffected as well as affected sibs, we introduce a new test statistic (referred to as TDS), which contrasts the allele frequency in affected sibs versus that estimated for the parents from the entire sibship. For sibships without parents, this test is analogous to the TDT and is completely robust to nonrandom mating patterns. The efficiency of the TDS test is comparable to that of the THS test (which compares affected vs. unaffected sibs and was based on DNA pooling), for sibships with one affected child. However, as the number of affected sibs in the sibship grows, the relative efficiency of the TDS test versus the THS test also increases. For example, for sibships with three affected, one-third fewer families are required; for families with four affected, nearly half as many are required. Thus, when sibships contain multiple affected individuals, the TDS test provides both an increase in power and robustness to nonrandom mating.