Valid Monte Carlo permutation tests for genetic case-control studies with missing genotypes.
Valid Monte Carlo permutation tests for genetic case-control studies with missing genotypes.
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有效的蒙特卡洛置换测试，用于基因型缺失的遗传病例对照研究。
DOI：
10.1002/gepi.21805
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发表时间：
2014-05
影响因子：
2.1
通讯作者：
Martin ER
中科院分区：
文献类型：
--
作者：
Kinnamon DD;Martin ER
蒙特卡罗排列检验可以通过选择一组个体指标的排列和测量基因型和情感状态之间关联的实值检验统计量来正式构建。在本文中，我们开发了一个严格的理论框架来验证这些测试的有效性时，有缺失的基因型。我们开始指定一个非参数概率模型的观察基因型数据的遗传病例对照研究与无关的主题。在这个模型和一些关于检验统计量的最小假设下，我们建立了所得到的MonteCarlo置换检验是精确水平α，如果（1）单个指标的置换集是一个复合群，（2）如果个体到行的分配根据零假设中的任意排列被打乱，则观察到的基因型得分矩阵的分布在零假设下不改变。选择集我们应用这些条件表明，经常使用的Monte Carlo置换测试的基础上的所有排列的个人指数的集合，保证是准确的水平α只有缺失数据过程满足一个相当严格的附加假设。然而，如果缺失数据处理依赖于所有已识别和记录的协变量，我们还证明了基于具有相同协变量值的个体层内排列集的Monte Carlo排列检验是精确水平α。我们的理论结果通过对各种缺失数据处理和测试统计的模拟进行了验证和补充。
Monte Carlo permutation tests can be formally constructed by choosing a set of permutations of individual indices and a real-valued test statistic measuring the association between genotypes and affection status. In this paper, we develop a rigorous theoretical framework for verifying the validity of these tests when there are missing genotypes. We begin by specifying a nonparametric probability model for the observed genotype data in a genetic case-control study with unrelated subjects. Under this model and some minimal assumptions about the test statistic, we establish that the resulting Monte Carlo permutation test is exact level α if (1) the set of permutations of individual indices is a group under composition and (2) the distribution of the observed genotype score matrix under the null hypothesis does not change if the assignment of individuals to rows is shuffled according to an arbitrary permutation in the chosen set. We apply these conditions to show that frequently used Monte Carlo permutation tests based on the set of all permutations of individual indices are guaranteed to be exact level α only for missing data processes satisfying a rather restrictive additional assumption. However, if the missing data process depends on covariates that are all identified and recorded, we also show that Monte Carlo permutation tests based on the set of permutations within strata of individuals with identical covariate values are exact level α. Our theoretical results are verified and supplemented by simulations for a variety of missing data processes and test statistics.
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影响因子：
3.7
作者：
Li L;Li Y;Browning SR;Browning BL;Slater AJ;Kong X;Aponte JL;Mooser VE;Chissoe SL;Whittaker JC;Nelson MR;Ehm MG
通讯作者：
Ehm MG
DOI：
10.1080/03610918.2012.625797
发表时间：
2012-01-01
影响因子：
0.9
作者：
Kennes, Lieven Nils;Hilgers, Ralf-Dieter;Heussen, Nicole
通讯作者：
Heussen, Nicole
影响因子：
--
作者：
DWASS, M
通讯作者：
DWASS, M
影响因子：
9.8
作者：
Kimmel, Gad;Jordan, Michael I.;Karp, Richard M.
通讯作者：
Karp, Richard M.
影响因子：
2.1
作者：
Chapman, Juliet;Whittaker, John
通讯作者：
Whittaker, John