An approximate model of polygenic inheritance.

Abstract

The finite polygenic model approximates polygenic inheritance by postulating that a quantitative trait is determined by n independent, additive loci. The 3n possible genotypes for each person in this model limit its applicability. CANNINGS, THOMPSON, and SKOLNICK suggested a simplified, nongenetic version of the model involving only 2n + 1 genotypes per person. This article shows that this hypergeometric polygenic model also approximates polygenic inheritance well. In particular, for noninbred pedigrees, trait means, variances, covariances, and marginal distributions match those of the ordinary finite polygenic model. Furthermore as n --> infinity, the trait values within a pedigree collectively tend toward multivariate normality. The implications of these results for likelihood evaluation under the polygenic threshold and mixed models of inheritance are discussed. Finally, a simple numerical example illustrates the application of the hypergeometric polygenic model to risk prediction under the polygenic threshold model.