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不同单核苷酸多态性基因型表型变异性的差异有什么意义?

What is the significance of difference in phenotypic variability across SNP genotypes?

机构信息

Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

出版信息

Am J Hum Genet. 2013 Aug 8;93(2):390-7. doi: 10.1016/j.ajhg.2013.06.017. Epub 2013 Aug 1.

Abstract

We studied the general problem of interpreting and detecting differences in phenotypic variability among the genotypes at a locus, from both a biological and a statistical point of view. The scales on which we measure interval-scale quantitative traits are man-made and have little intrinsic biological relevance. Before claiming a biological interpretation for genotype differences in variance, we should be sure that no monotonic transformation of the data can reduce or eliminate these differences. We show theoretically that for an autosomal diallelic SNP, when the three corresponding means are distinct so that the variance can be expressed as a quadratic function of the mean, there implicitly exists a transformation that will tend to equalize the three variances; we also demonstrate how to find a transformation that will do this. We investigate the validity of Bartlett's test, Box's modification of it, and a modified Levene's test to test for differences in variances when normality does not hold. We find that, although they may detect differences in variability, these tests do not necessarily detect differences in variance. The same is true for permutation tests that use these three statistics.

摘要

我们从生物学和统计学两个角度研究了在一个基因座的基因型之间表型变异性差异的解释和检测的一般问题。我们用于测量定距尺度数量性状的尺度是人为的,与内在的生物学相关性不大。在声称基因型方差差异具有生物学意义之前,我们应该确定没有单调变换数据可以减少或消除这些差异。我们从理论上证明,对于常染色体双等位 SNP,当三个对应的均值不同,使得方差可以表示为均值的二次函数时,隐式地存在一种变换,这种变换将趋于使三个方差相等;我们还演示了如何找到这样的变换。我们研究了 Bartlett 检验、Box 对其的修正以及 modified Levene's 检验在不满足正态性时用于检验方差差异的有效性。我们发现,尽管这些检验可能会检测到变异性的差异,但它们不一定会检测到方差的差异。对于使用这三个统计量的置换检验也是如此。

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