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回归法和最大似然法用于从同胞对和异卵双生子数据中定位数量性状基因座的效能。

Power of regression and maximum likelihood methods to map QTL from sib-pair and DZ twin data.

作者信息

Visscher P M, Hopper J L

机构信息

Centre for Genetic Epidemiology, The University of Melbourne, Australia.

出版信息

Ann Hum Genet. 2001 Nov;65(Pt 6):583-601. doi: 10.1017/S0003480001008909.

Abstract

A common study design to map quantitative trait loci (QTL) is to compare the phenotypes and marker genotypes of two or more siblings in a sample of unrelated sib groups, and to test for linkage between chromosome location and quantitative trait values. The simplest case is sib pairs only, in particular dizygotic twin pairs, and a simple and elegant regression method was proposed by Haseman & Elston in 1972 to test for linkage. Since then, several other methods have been proposed to test for linkage. In this study, we derived the statistical power of linear regression and maximum likelihood methods to map QTL from sib pair data analytically, and determined which methods are superior under which set of population parameters. In particular, we considered four regression-based and three maximum likelihood-based approaches, and derived asymptotic approximations of the mean test statistic and statistical power for each method. It was found, both analytically and by computer simulation, that the revisited or new Haseman-Elston method (based upon the mean-corrected crossproduct of the observations on sib-pairs) is less powerful than a full maximum likelihood approach and is also inferior to the Haseman-Elston method under a realistic range of values for the population parameters. We found that a simple regression method, based upon both the squared difference and the mean-corrected squared sum of the observations on sib-pairs, is as powerful as a full maximum likelihood approach. Our derivations of statistical power for regression and maximum likelihood methods provide a simple way to compare alternative methods and obviate the need to perform elaborate computer simulations. DZ twin pairs are likely to be more powerful for linkage analysis than ordinary siblings because they may share more common environmental effects, thereby increasing the proportion of within-family variance that is explained by a QTL.

摘要

一种用于定位数量性状基因座(QTL)的常见研究设计是,在无关同胞组样本中比较两个或更多同胞的表型和标记基因型,并检验染色体位置与数量性状值之间的连锁关系。最简单的情况是仅使用同胞对,特别是异卵双胞胎对,1972年哈斯曼和埃尔斯顿提出了一种简单而优雅的回归方法来检验连锁关系。从那时起,又提出了其他几种检验连锁关系的方法。在本研究中,我们通过分析得出了线性回归和最大似然法从同胞对数据中定位QTL的统计功效,并确定了在哪些总体参数集下哪种方法更优。特别是,我们考虑了四种基于回归的方法和三种基于最大似然的方法,并得出了每种方法的平均检验统计量和统计功效的渐近近似值。通过分析和计算机模拟发现,重新审视的或新的哈斯曼 - 埃尔斯顿方法(基于同胞对观测值的均值校正交叉乘积)比完全最大似然法的功效更低,并且在总体参数的实际取值范围内也不如哈斯曼 - 埃尔斯顿方法。我们发现,一种基于同胞对观测值的平方差和均值校正平方和的简单回归方法与完全最大似然法的功效相同。我们对回归和最大似然法统计功效的推导提供了一种比较替代方法的简单途径,无需进行复杂的计算机模拟。异卵双胞胎对在连锁分析中可能比普通同胞更具功效,因为它们可能共享更多共同的环境效应,从而增加了由QTL解释的家系内方差比例。

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