A class of Bayesian methods to combine large numbers of genotyped and non-genotyped animals for whole-genome analyses

Genet Sel Evol. 2014 Sep 22;46(1):50. doi: 10.1186/1297-9686-46-50.

Abstract

Background: To obtain predictions that are not biased by selection, the conditional mean of the breeding values must be computed given the data that were used for selection. When single nucleotide polymorphism (SNP) effects have a normal distribution, it can be argued that single-step best linear unbiased prediction (SS-BLUP) yields a conditional mean of the breeding values. Obtaining SS-BLUP, however, requires computing the inverse of the dense matrix G of genomic relationships, which will become infeasible as the number of genotyped animals increases. Also, computing G requires the frequencies of SNP alleles in the founders, which are not available in most situations. Furthermore, SS-BLUP is expected to perform poorly relative to variable selection models such as BayesB and BayesC as marker densities increase.

Methods: A strategy is presented for Bayesian regression models (SSBR) that combines all available data from genotyped and non-genotyped animals, as in SS-BLUP, but accommodates a wider class of models. Our strategy uses imputed marker covariates for animals that are not genotyped, together with an appropriate residual genetic effect to accommodate deviations between true and imputed genotypes. Under normality, one formulation of SSBR yields results identical to SS-BLUP, but does not require computing G or its inverse and provides richer inferences. At present, Bayesian regression analyses are used with a few thousand genotyped individuals. However, when SSBR is applied to all animals in a breeding program, there will be a 100 to 200-fold increase in the number of animals and an associated 100 to 200-fold increase in computing time. Parallel computing strategies can be used to reduce computing time. In one such strategy, a 58-fold speedup was achieved using 120 cores.

Discussion: In SSBR and SS-BLUP, phenotype, genotype and pedigree information are combined in a single-step. Unlike SS-BLUP, SSBR is not limited to normally distributed marker effects; it can be used when marker effects have a t distribution, as in BayesA, or mixture distributions, as in BayesB or BayesC π. Furthermore, it has the advantage that matrix inversion is not required. We have investigated parallel computing to speedup SSBR analyses so they can be used for routine applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Bayes Theorem
  • Breeding
  • Gene Frequency
  • Genetic Association Studies / veterinary*
  • Genomics / methods
  • Genotype*
  • Genotyping Techniques / veterinary
  • Models, Genetic
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide