A non-parametric mixture model for genome-enabled prediction of genetic value for a quantitative trait.
A Bayesian nonparametric form of regression based on Dirichlet process priors is adapted to the analysis of quantitative traits possibly affected by cryptic forms of gene action, and to the context of SNP-assisted genomic selection, where the main objective is to predict a genomic signal on phenotype. The procedure clusters unknown genotypes into groups with distinct genetic values, but in a setting in which the number of clusters is unknown a priori, so that standard methods for finite mixture analysis do not work. The central assumption is that genetic effects follow an unknown distribution with some "baseline" family, which is a normal process in the cases considered here. A Bayesian analysis based on the Gibbs sampler produces estimates of the number of clusters, posterior means of genetic effects, a measure of credibility in the baseline distribution, as well as estimates of parameters of the latter. The procedure is illustrated with a simulation representing two populations. In the first one, there are 3 unknown QTL, with additive, dominance and epistatic effects; in the second, there are 10 QTL with additive, dominance and additive × additive epistatic effects. In the two populations, baseline parameters are inferred correctly. The Dirichlet process model infers the number of unique genetic values correctly in the first population, but it produces an understatement in the second one; here, the true number of clusters is over 900, and the model gives a posterior mean estimate of about 140, probably because more replication of genotypes is needed for correct inference. The impact on inferences of the prior distribution of a key parameter (M), and of the extent of replication, was examined via an analysis of mean body weight in 192 paternal half-sib families of broiler chickens, where each sire was genotyped for nearly 7,000 SNPs. In this small sample, it was found that inference about the number of clusters was affected by the prior distribution of M. For a set of combinations of parameters of a given prior distribution, the effects of the prior dissipated when the number of replicate samples per genotype was increased. Thus, the Dirichlet process model seems to be useful for gauging the number of QTLs affecting the trait: if the number of clusters inferred is small, probably just a few QTLs code for the trait. If the number of clusters inferred is large, this may imply that standard parametric models based on the baseline distribution may suffice. However, priors may be influential, especially if sample size is not large and if only a few genotypic configurations have replicate phenotypes in the sample.
Gianola
Daniel
D
Department of Animal Sciences and Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Dr, Madison, WI 53706, USA. gianola@ansci.wisc.edu
Wu
Xiao-Lin
XL
Manfredi
Eduardo
E
Simianer
Henner
H
D001499:Bayes Theorem; D004843:Epistasis, Genetic; D005819:Genetic Markers; D016678:Genome; D005838:Genotype; D016013:Likelihood Functions; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D018401:Sample Size
D005819:Genetic Markers