Accuracy of Whole-Genome Prediction Using a Genetic Architecture-Enhanced Variance-Covariance Matrix

Obtaining accurate predictions of unobserved genetic or phenotypic values for complex traits in animal, plant, and human populations is possible through whole-genome prediction (WGP), a combined analysis of genotypic and phenotypic data. Because the underlying genetic architecture of the trait of interest is an important factor affecting model selection, we propose a new strategy, termed BLUP|GA (BLUP-given genetic architecture), which can use genetic architecture information within the dataset at hand rather than from public sources. This is achieved by using a trait-specific covariance matrix (T), which is a weighted sum of a genetic architecture part (S matrix) and the realized relationship matrix (G). The algorithm of BLUP|GA (BLUP-given genetic architecture) is provided and illustrated with real and simulated datasets. Predictive ability of BLUP|GA was validated with three model traits in a dairy cattle dataset and 11 traits in three public datasets with a variety of genetic architectures and compared with GBLUP and other approaches. Results show that BLUP|GA outperformed GBLUP in 20 of 21 scenarios in the dairy cattle dataset and outperformed GBLUP, BayesA, and BayesB in 12 of 13 traits in the analyzed public datasets. Further analyses showed that the difference of accuracies for BLUP|GA and GBLUP significantly correlate with the distance between the T and G matrices. The new strategy applied in BLUP|GA is a favorable and flexible alternative to the standard GBLUP model, allowing to account for the genetic architecture of the quantitative trait under consideration when necessary. This feature is mainly due to the increased similarity between the trait-specific relationship matrix (T matrix) and the genetic relationship matrix at unobserved causal loci. Applying BLUP|GA in WGP would ease the burden of model selection.

[1]  M. Goddard,et al.  Prediction of total genetic value using genome-wide dense marker maps. , 2001, Genetics.

[2]  D. Allison,et al.  A Comprehensive Genetic Approach for Improving Prediction of Skin Cancer Risk in Humans , 2012, Genetics.

[3]  D. de Koning,et al.  Accuracy of genomic prediction using low-density marker panels. , 2011, Journal of dairy science.

[4]  T. A. Martin,et al.  Accuracy of Genomic Selection Methods in a Standard Data Set of Loblolly Pine (Pinus taeda L.) , 2012, Genetics.

[5]  M. Calus,et al.  Whole-Genome Regression and Prediction Methods Applied to Plant and Animal Breeding , 2013, Genetics.

[6]  Zhe Zhang,et al.  Best Linear Unbiased Prediction of Genomic Breeding Values Using a Trait-Specific Marker-Derived Relationship Matrix , 2010, PloS one.

[7]  R. Fernando,et al.  Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor , 2013, PLoS genetics.

[8]  C. R. Henderson,et al.  Best linear unbiased estimation and prediction under a selection model. , 1975, Biometrics.

[9]  C. R. Henderson Rapid Method for Computing the Inverse of a Relationship Matrix , 1975 .

[10]  Guosheng Su,et al.  A common reference population from four European Holstein populations increases reliability of genomic predictions , 2011, Genetics Selection Evolution.

[11]  F. Seefried,et al.  Impacts of both reference population size and inclusion of a residual polygenic effect on the accuracy of genomic prediction , 2011, Genetics Selection Evolution.

[12]  Xiaolin Wu,et al.  Animal QTLdb: an improved database tool for livestock animal QTL/association data dissemination in the post-genome era , 2012, Nucleic Acids Res..

[13]  I Misztal,et al.  Hot topic: a unified approach to utilize phenotypic, full pedigree, and genomic information for genetic evaluation of Holstein final score. , 2010, Journal of dairy science.

[14]  P. VanRaden,et al.  Efficient methods to compute genomic predictions. , 2008, Journal of dairy science.

[15]  Daniel Gianola,et al.  Predicting genetic predisposition in humans: the promise of whole-genome markers , 2010, Nature Reviews Genetics.

[16]  J. Woolliams,et al.  The Impact of Genetic Architecture on Genome-Wide Evaluation Methods , 2010, Genetics.

[17]  P. VanRaden,et al.  Invited review: reliability of genomic predictions for North American Holstein bulls. , 2009, Journal of dairy science.

[18]  Ole F. Christensen,et al.  Proceedings, 10 World Congress of Genetics Applied to Livestock Production DMU - A Package for Analyzing Multivariate Mixed Models in quantitative Genetics and Genomics , 2014 .

[19]  Daniel Gianola,et al.  Using Whole-Genome Sequence Data to Predict Quantitative Trait Phenotypes in Drosophila melanogaster , 2012, PLoS genetics.

[20]  Timothy P. L. Smith,et al.  Development and Characterization of a High Density SNP Genotyping Assay for Cattle , 2009, PloS one.

[21]  F. Dudbridge Power and Predictive Accuracy of Polygenic Risk Scores , 2013, PLoS genetics.

[22]  Daniel Gianola,et al.  Additive Genetic Variability and the Bayesian Alphabet , 2009, Genetics.

[23]  M. Stitt,et al.  Genomic and metabolic prediction of complex heterotic traits in hybrid maize , 2012, Nature Genetics.

[24]  John M. Hickey,et al.  A Common Dataset for Genomic Analysis of Livestock Populations , 2012, G3: Genes | Genomes | Genetics.

[25]  Guosheng Su,et al.  Comparison on genomic predictions using three GBLUP methods and two single-step blending methods in the Nordic Holstein population , 2012, Genetics Selection Evolution.

[26]  R. Fernando,et al.  Breeding value prediction for production traits in layer chickens using pedigree or genomic relationships in a reduced animal model , 2011, Genetics Selection Evolution.

[27]  R. Fernando,et al.  Genome-wide association mapping including phenotypes from relatives without genotypes in a single-step (ssGWAS) for 6-week body weight in broiler chickens , 2014, Front. Genet..

[28]  M. Goddard,et al.  Accurate Prediction of Genetic Values for Complex Traits by Whole-Genome Resequencing , 2010, Genetics.

[29]  J. Hickey,et al.  Simulated Data for Genomic Selection and Genome-Wide Association Studies Using a Combination of Coalescent and Gene Drop Methods , 2012, G3: Genes | Genomes | Genetics.

[30]  D. de Koning,et al.  Setting the Standard: A Special Focus on Genomic Selection in GENETICS and G3 , 2012, G3: Genes | Genomes | Genetics.

[31]  M. Goddard,et al.  Genetic Architecture of Complex Traits and Accuracy of Genomic Prediction: Coat Colour, Milk-Fat Percentage, and Type in Holstein Cattle as Contrasting Model Traits , 2010, PLoS genetics.

[32]  H. Kadarmideen Genomics to systems biology in animal and veterinary sciences: Progress, lessons and opportunities☆ , 2014 .

[33]  M. Calus,et al.  Genomic Prediction in Animals and Plants: Simulation of Data, Validation, Reporting, and Benchmarking , 2013, Genetics.

[34]  Yu Wang,et al.  Genome-Wide Prediction of Traits with Different Genetic Architecture Through Efficient Variable Selection , 2013, Genetics.

[35]  Xiangdong Ding,et al.  Accuracy of genomic prediction for milk production traits in the Chinese Holstein population using a reference population consisting of cows. , 2013, Journal of dairy science.

[36]  M. Goddard,et al.  Mapping genes for complex traits in domestic animals and their use in breeding programmes , 2009, Nature Reviews Genetics.

[37]  P. Visscher,et al.  Increased accuracy of artificial selection by using the realized relationship matrix. , 2009, Genetics research.

[38]  T. H. E. Meuwissen,et al.  Marker based estimates of between and within population kinships for the conservation of genetic diversity , 2001 .

[39]  Ismo Strandén,et al.  Allele coding in genomic evaluation , 2011, Genetics Selection Evolution.

[40]  Zhe Zhang,et al.  Advances in genomic selection in domestic animals , 2011 .

[41]  R. Sederoff,et al.  Detection of a major gene for resistance to fusiform rust disease in loblolly pine by genomic mapping. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Sang Hong Lee,et al.  Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data , 2008, PLoS genetics.

[43]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[44]  Zhe Zhang,et al.  Improving the Accuracy of Whole Genome Prediction for Complex Traits Using the Results of Genome Wide Association Studies , 2014, PloS one.

[45]  William H Briggs,et al.  Accuracy of Across-Environment Genome-Wide Prediction in Maize Nested Association Mapping Populations , 2013, G3: Genes | Genomes | Genetics.

[46]  D. Garrick,et al.  Technical note: Derivation of equivalent computing algorithms for genomic predictions and reliabilities of animal merit. , 2009, Journal of dairy science.

[47]  I Misztal,et al.  Computing procedures for genetic evaluation including phenotypic, full pedigree, and genomic information. , 2009, Journal of dairy science.

[48]  D. Neale,et al.  Patterns of Population Structure and Environmental Associations to Aridity Across the Range of Loblolly Pine (Pinus taeda L., Pinaceae) , 2010, Genetics.

[49]  Frank Technow,et al.  Comparison of whole-genome prediction models for traits with contrasting genetic architecture in a diversity panel of maize inbred lines , 2012, BMC Genomics.

[50]  M. Stone Cross‐Validatory Choice and Assessment of Statistical Predictions , 1976 .