Bochud Murielle
Institute of Social and Preventive Medicine, Lausanne University Hospital, Route de la Corniche 10, 1010, Lausanne, Switzerland.
Methods Mol Biol. 2017;1666:195-210. doi: 10.1007/978-1-4939-7274-6_10.
Heritability is a measure of familial resemblance. Estimating the heritability of a trait could be one of the first steps in the gene mapping process. This chapter describes how to estimate heritability for quantitative traits from nuclear and pedigree data using the ASSOC program in the Statistical Analysis in Genetic Epidemiology (S.A.G.E.) software package. Estimating heritability rests on the assumption that the total phenotypic variance of a quantitative trait can be partitioned into independent genetic and environmental components. In turn, the genetic variance can be divided into an additive (polygenic) genetic variance, a dominance variance (nonlinear interaction effects between alleles at the same locus) and an epistatic variance (interaction effects between alleles at different loci). The last two are often assumed to be zero. The additive genetic variance represents the average effects of individual alleles on the phenotype and reflects transmissible resemblance between relatives. Heritability in the narrow sense (h ) refers to the ratio of the additive genetic variance to the total phenotypic variance. Heritability is a dimensionless population-specific parameter. ASSOC estimates association parameters (regression coefficients) and variance components from family data. ASSOC uses a linear regression model in which the total residual variance is partitioned, after regressing on covariates, into the sum of random components such as an additive polygenic component, a random sibship component, random nuclear family components, a random marital component, and an individual-specific random component. Assortative mating, nonrandom ascertainment of families, and failure to account for key confounding factors may bias heritability estimates.
遗传力是家族相似性的一种度量。估计一个性状的遗传力可能是基因定位过程的首要步骤之一。本章描述了如何使用遗传流行病学统计分析（S.A.G.E.）软件包中的ASSOC程序，从核心家系和系谱数据估计数量性状的遗传力。估计遗传力基于这样一个假设，即数量性状的总表型方差可以划分为独立的遗传和环境成分。反过来，遗传方差又可以分为加性（多基因）遗传方差、显性方差（同一基因座上等位基因之间的非线性相互作用效应）和上位性方差（不同基因座上等位基因之间的相互作用效应）。通常假定后两者为零。加性遗传方差代表单个等位基因对表型的平均效应，并反映亲属之间的可传递相似性。狭义遗传力（h ）指加性遗传方差与总表型方差的比率。遗传力是一个无量纲的群体特异性参数。ASSOC从家系数据估计关联参数（回归系数）和方差成分。ASSOC使用线性回归模型，在对协变量进行回归后，总残差方差被划分为随机成分之和，如加性多基因成分、随机同胞成分、随机核心家系成分、随机婚姻成分和个体特异性随机成分。选型交配、家系的非随机确定以及未能考虑关键混杂因素可能会使遗传力估计产生偏差。
