Informative missingness in genetic association studies: Case-parent designs
Informative missingness in genetic association studies: Case-parent designs
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DOI：
10.1086/368276
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发表时间：
2003-03-01
影响因子：
9.8
通讯作者：
Satten, GA
中科院分区：
文献类型：
--
作者：
Allen, AS;Rathouz, PJ;Satten, GA
我们考虑了信息缺失对关联测试的影响，这些测试使用父母的基因类型作为对照，并允许丢失父母的数据。当父母可供研究的概率与该父母的基因有关时，父母数据可能会信息缺失；当发生这种情况时，观察到的父母中的基因类型分布不能代表丢失的父母中的基因类型分布。许多以前提出的允许缺失父母数据的程序假设这些分布是相同的。我们提出了当父母数据信息缺失时表现良好的关联测试，假设对于给定的三个父亲、母亲和受影响的后代基因类型，父母的基因类型和缺失父母的性别，而不是受影响子女的基因，可以影响父母的缺失。(对于忽略不完整的亲子三人组的分析的有效性，同样的假设也是必需的。)我们使用模拟来比较我们的方法与以前提出的程序，我们表明，即使是少量的信息缺失没有被考虑在内，它们也可能对测试的性能产生巨大的有害影响。
We consider the effect of informative missingness on association tests that use parental genotypes as controls and that allow for missing parental data. Parental data can be informatively missing when the probability of a parent being available for study is related to that parent's genotype; when this occurs, the distribution of genotypes among observed parents is not representative of the distribution of genotypes among the missing parents. Many previously proposed procedures that allow for missing parental data assume that these distributions are the same. We propose association tests that behave well when parental data are informatively missing, under the assumption that, for a given trio of paternal, maternal, and affected offspring genotypes, the genotypes of the parents and the sex of the missing parents, but not the genotype of the affected offspring, can affect parental missingness. (This same assumption is required for validity of an analysis that ignores incomplete parent-offspring trios.) We use simulations to compare our approach with previously proposed procedures, and we show that if even small amounts of informative missingness are not taken into account, they can have large, deleterious effects on the performance of tests.