A robust mean and variance test with application to high-dimensional phenotypes.
A robust mean and variance test with application to high-dimensional phenotypes.
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DOI：
10.1007/s10654-021-00805-w
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发表时间：
2022-04
影响因子：
13.6
通讯作者：
Tilling, Kate
中科院分区：
文献类型：
--
作者：
Staley, James R.;Windmeijer, Frank;Suderman, Matthew;Lyon, Matthew S.;Davey Smith, George;Tilling, Kate
大多数关于连续健康相关结果的研究都检查了不同暴露的结果平均水平（位置）的差异。然而，识别对结果的可变性（规模）的影响，并结合平均值和可变性（位置和规模）的测试，可以提供更多的生物学机制的见解。联合测试可以提高高维表型研究的能力，例如CpG位点DNA甲基化的表观基因组关联研究。方差异质性的一个可能原因是一个变量在其对结果的影响中与暴露相互作用，因此均值和变异性的联合检验有助于识别效应修饰因子。在这里，我们回顾了规模测试，布朗-福赛斯测试的基础上，分析连续的结果与分类和连续曝光的变异性，并开发了一种新的联合位置和规模评分（JLSsc）测试。将这些测试与模拟中的替代方法进行比较，并使用来自综合表观基因组学研究可扩展资源（ARIES）的数据来测试DNA甲基化的平均值和变异性与性别和胎龄的关联。在模拟中，Brown-Forsythe和JLSsc测试保留正确的I型错误率时，结果不是正态分布的，相反，其他方法测试，都有膨胀的I型错误率。这些测试还鉴定了> 7500个CpG位点，其脐带血甲基化的平均值或变异性根据性别或胎龄而不同。Brown-Forsythe检验和JLSsc是稳健的检验，可用于检测不仅仅由平均效应驱动的关联。在线版本包含补充材料，可通过10.1007/s10654-021-00805-w获得。
Most studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect. The online version contains supplementary material available at 10.1007/s10654-021-00805-w.
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影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
3.7
作者：
GLEJSER, H
通讯作者：
GLEJSER, H
DOI：
10.1098/rspa.1937.0109
发表时间：
1937-05-01
影响因子：
--
作者：
Bartlett, MS
通讯作者：
Bartlett, MS
影响因子：
7.7
作者：
Relton CL;Gaunt T;McArdle W;Ho K;Duggirala A;Shihab H;Woodward G;Lyttleton O;Evans DM;Reik W;Paul YL;Ficz G;Ozanne SE;Wipat A;Flanagan K;Lister A;Heijmans BT;Ring SM;Davey Smith G
通讯作者：
Davey Smith G
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.