Abney M, McPeek M S, Ober C
Department of Human Genetics, University of Chicago, 924 East 57th Street, R-102, Chicago, IL 60637, USA.
Am J Hum Genet. 2000 Feb;66(2):629-50. doi: 10.1086/302759.
Use of variance-component estimation for mapping of quantitative-trait loci in humans is a subject of great current interest. When only trait values, not genotypic information, are considered, variance-component estimation can also be used to estimate heritability of a quantitative trait. Inbred pedigrees present special challenges for variance-component estimation. First, there are more variance components to be estimated in the inbred case, even for a relatively simple model including additive, dominance, and environmental effects. Second, more identity coefficients need to be calculated from an inbred pedigree in order to perform the estimation, and these are computationally more difficult to obtain in the inbred than in the outbred case. As a result, inbreeding effects have generally been ignored in practice. We describe here the calculation of identity coefficients and estimation of variance components of quantitative traits in large inbred pedigrees, using the example of HDL in the Hutterites. We use a multivariate normal model for the genetic effects, extending the central-limit theorem of Lange to allow for both inbreeding and dominance under the assumptions of our variance-component model. We use simulated examples to give an indication of under what conditions one has the power to detect the additional variance components and to examine their impact on variance-component estimation. We discuss the implications for mapping and heritability estimation by use of variance components in inbred populations.
利用方差分量估计法对人类数量性状位点进行定位是当前备受关注的课题。当仅考虑性状值而非基因型信息时，方差分量估计法也可用于估计数量性状的遗传力。近交家系给方差分量估计带来了特殊挑战。首先，即使对于一个相对简单的包含加性、显性和环境效应的模型，在近交情况下需要估计的方差分量更多。其次，为了进行估计，需要从近交家系中计算更多的亲缘系数，而且在近交情况下这些系数的计算在计算上比非近交情况更困难。因此，在实际中近交效应通常被忽略。我们在此以哈特派人群中高密度脂蛋白为例，描述在大型近交家系中亲缘系数的计算以及数量性状方差分量的估计。我们对遗传效应使用多元正态模型，扩展了兰格的中心极限定理，以在我们的方差分量模型假设下同时考虑近交和显性。我们使用模拟示例来说明在何种条件下能够检测到额外的方差分量，并检验它们对方差分量估计的影响。我们讨论了在近交群体中使用方差分量进行定位和遗传力估计的意义。
