Variance heterogeneity analysis for detection of potentially interacting genetic loci: method and its limitations.
Variance heterogeneity analysis for detection of potentially interacting genetic loci: method and its limitations.
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DOI：
10.1186/1471-2156-11-92
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发表时间：
2010-10-13
期刊：
影响因子：
2.9
通讯作者：
Aulchenko YS
中科院分区：
文献类型：
--
作者：
Struchalin MV;Dehghan A;Witteman JC;van Duijn C;Aulchenko YS
在决定某一性状的值时，某一基因和某些因素之间存在交互作用，因此，在具有该基因的受试者群体中，该性状的变异量会增加。因此，方差异质性检验可用于筛选潜在的相互作用的单核苷酸多态(SNPs)。在这项工作中，我们评估了在相互作用变量未知的情况下，关于检测潜在相互作用的SNPs的方差异质性分析的统计特性。通过模拟，我们研究了Bartlett检验、性状到正态分布的先验等级变换的Bartlett检验以及不同遗传模型的Levene检验的I类误差。此外，我们还推导了功率估计的解析表达式。我们表明，在性状服从正态分布的情况下，Bartlett检验具有可接受的I型误差，而Levene检验在所研究的所有情景下保持名义I型误差。对于方差齐性检验，我们证明了(与使用已知交互作用因素信息的直接检验相反)，在给定相同的交互作用的情况下，根据未观察到的交互作用变量的不可估量的直接影响，该作用可以有很大的变化。因此，对于给定的交互作用效应，只能估计方差齐性检验的非常宽的功率范围。我们还应用Levene的方法在鹿特丹研究人群(n=5959)中测试了C-反应蛋白变异的全基因组同质性。在这项分析中，我们复制了Pare和他的同事(2010)对SNP rs12753193(n=21,799)的先前结果。筛选SNP不同基因型间的差异是一种很有前途的方法，因为许多生物学上有趣的模型可能导致差异的异质性。然而，应当记住，SNP没有方差异质性不能解释为SNP在相互作用网络中没有参与。
Presence of interaction between a genotype and certain factor in determination of a trait's value, it is expected that the trait's variance is increased in the group of subjects having this genotype. Thus, test of heterogeneity of variances can be used as a test to screen for potentially interacting single-nucleotide polymorphisms (SNPs). In this work, we evaluated statistical properties of variance heterogeneity analysis in respect to the detection of potentially interacting SNPs in a case when an interaction variable is unknown. Through simulations, we investigated type I error for Bartlett's test, Bartlett's test with prior rank transformation of a trait to normality, and Levene's test for different genetic models. Additionally, we derived an analytical expression for power estimation. We showed that Bartlett's test has acceptable type I error in the case of trait following a normal distribution, whereas Levene's test kept nominal Type I error under all scenarios investigated. For the power of variance homogeneity test, we showed (as opposed to the power of direct test which uses information about known interacting factor) that, given the same interaction effect, the power can vary widely depending on the non-estimable direct effect of the unobserved interacting variable. Thus, for a given interaction effect, only very wide limits of power of the variance homogeneity test can be estimated. Also we applied Levene's approach to test genome-wide homogeneity of variances of the C-reactive protein in the Rotterdam Study population (n = 5959). In this analysis, we replicate previous results of Pare and colleagues (2010) for the SNP rs12753193 (n = 21, 799). Screening for differences in variances among genotypes of a SNP is a promising approach as a number of biologically interesting models may lead to the heterogeneity of variances. However, it should be kept in mind that the absence of variance heterogeneity for a SNP can not be interpreted as the absence of involvement of the SNP in the interaction network.
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DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.
影响因子：
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影响因子：
4.5
作者：
Paré G;Cook NR;Ridker PM;Chasman DI
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Chasman DI
DOI：
10.1146/annurev.genom.9.081307.164242
发表时间：
2009
影响因子：
8.7
作者：
Li Y;Willer C;Sanna S;Abecasis G
通讯作者：
Abecasis G
影响因子：
5.2
作者：
Aulchenko, Yurii S.;Struchalin, Maksim V.;Borodin, Pavel M.
通讯作者：
Borodin, Pavel M.