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遗传力曲线:家族模型中遗传力的局部度量。

Heritability curves: A local measure of heritability in family models.

作者信息

Berentsen Geir D, Azzolini Francesca, Skaug Hans J, Lie Rolv T, Gjessing Håkon K

机构信息

Department of Business and Management Science, NHH Norwegian School of Economics, Bergen, Norway.

Department of Mathematics, University of Bergen, Bergen, Norway.

出版信息

Stat Med. 2021 Mar 15;40(6):1357-1382. doi: 10.1002/sim.8845. Epub 2020 Dec 17.

Abstract

Classical heritability models for family data split the phenotype variance into genetic and environmental components. For instance, the ACE model in twin studies assumes the phenotype variance decomposes as a  + c  + e , representing (additive) genetic effects, common (shared) environment, and residual environment, respectively. However, for some phenotypes it is biologically plausible that the genetic and environmental components may vary over the range of the phenotype. For instance, very large or small values of the phenotype may be caused by "sporadic" environmental factors, whereas the mid-range phenotype variation may be more under the control of common genetic factors. This article introduces a "local" measure of heritability, where the genetic and environmental components are allowed to depend on the value of the phenotype itself. Our starting point is a general formula for local correlation between two random variables. For estimation purposes, we use a multivariate Gaussian mixture, which is able to capture nonlinear dependence and respects certain distributional constraints. We derive an analytical expression for the associated correlation curve, and show how to decompose the correlation curve into genetic and environmental parts, for instance, a (y) + c (y) + e (y) for the ACE model, where we estimate the components as functions of the phenotype y. Furthermore, our model allows switching, for instance, from the ACE model to the ADE model within the range of the same phenotype. When applied to birth weight (BW) data on Norwegian mother-father-child trios, we conclude from the model that low and high BW are less heritable traits than medium BW. We also demonstrate switching between the ACE and ADE model when studying body mass index in adult monozygotic and dizygotic twins.

摘要

用于家庭数据的经典遗传力模型将表型方差分解为遗传和环境成分。例如,双胞胎研究中的ACE模型假设表型方差分解为a + c + e,分别代表(加性)遗传效应、共同(共享)环境和残余环境。然而,对于某些表型,遗传和环境成分可能在表型范围内变化,这在生物学上是合理的。例如,表型的非常大或非常小的值可能由“偶发性”环境因素引起,而中等范围的表型变异可能更多地受常见遗传因素的控制。本文介绍了一种“局部”遗传力度量,其中遗传和环境成分被允许依赖于表型本身的值。我们的出发点是两个随机变量之间局部相关性的一般公式。为了进行估计,我们使用多元高斯混合模型,它能够捕捉非线性依赖性并符合某些分布约束。我们推导了相关相关曲线的解析表达式,并展示了如何将相关曲线分解为遗传和环境部分,例如,对于ACE模型为a(y) + c(y) + e(y),其中我们将这些成分估计为表型y的函数。此外,我们的模型允许在同一表型范围内进行切换,例如从ACE模型切换到ADE模型。当应用于挪威父母-子女三人组的出生体重(BW)数据时,我们从模型中得出结论,低出生体重和高出生体重的遗传力特征低于中等出生体重。我们还展示了在研究成年同卵和异卵双胞胎的体重指数时,ACE模型和ADE模型之间的切换。

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