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Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data

Genome-wide association studies (GWAS) for quantitative traits and disease in humans and other species have shown that there are many loci that contribute to the observed resemblance between relatives. GWAS to date have mostly focussed on discovery of genes or regulatory regions habouring causative...

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Autores principales: Lee, Sang Hong, van der Werf, Julius H. J., Hayes, Ben J., Goddard, Michael E., Visscher, Peter M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565502/
https://www.ncbi.nlm.nih.gov/pubmed/18949033
http://dx.doi.org/10.1371/journal.pgen.1000231
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author Lee, Sang Hong
van der Werf, Julius H. J.
Hayes, Ben J.
Goddard, Michael E.
Visscher, Peter M.
author_facet Lee, Sang Hong
van der Werf, Julius H. J.
Hayes, Ben J.
Goddard, Michael E.
Visscher, Peter M.
author_sort Lee, Sang Hong
collection PubMed
description Genome-wide association studies (GWAS) for quantitative traits and disease in humans and other species have shown that there are many loci that contribute to the observed resemblance between relatives. GWAS to date have mostly focussed on discovery of genes or regulatory regions habouring causative polymorphisms, using single SNP analyses and setting stringent type-I error rates. Genome-wide marker data can also be used to predict genetic values and therefore predict phenotypes. Here, we propose a Bayesian method that utilises all marker data simultaneously to predict phenotypes. We apply the method to three traits: coat colour, %CD8 cells, and mean cell haemoglobin, measured in a heterogeneous stock mouse population. We find that a model that contains both additive and dominance effects, estimated from genome-wide marker data, is successful in predicting unobserved phenotypes and is significantly better than a prediction based upon the phenotypes of close relatives. Correlations between predicted and actual phenotypes were in the range of 0.4 to 0.9 when half of the number of families was used to estimate effects and the other half for prediction. Posterior probabilities of SNPs being associated with coat colour were high for regions that are known to contain loci for this trait. The prediction of phenotypes using large samples, high-density SNP data, and appropriate statistical methodology is feasible and can be applied in human medicine, forensics, or artificial selection programs.
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spelling pubmed-25655022008-10-24 Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data Lee, Sang Hong van der Werf, Julius H. J. Hayes, Ben J. Goddard, Michael E. Visscher, Peter M. PLoS Genet Research Article Genome-wide association studies (GWAS) for quantitative traits and disease in humans and other species have shown that there are many loci that contribute to the observed resemblance between relatives. GWAS to date have mostly focussed on discovery of genes or regulatory regions habouring causative polymorphisms, using single SNP analyses and setting stringent type-I error rates. Genome-wide marker data can also be used to predict genetic values and therefore predict phenotypes. Here, we propose a Bayesian method that utilises all marker data simultaneously to predict phenotypes. We apply the method to three traits: coat colour, %CD8 cells, and mean cell haemoglobin, measured in a heterogeneous stock mouse population. We find that a model that contains both additive and dominance effects, estimated from genome-wide marker data, is successful in predicting unobserved phenotypes and is significantly better than a prediction based upon the phenotypes of close relatives. Correlations between predicted and actual phenotypes were in the range of 0.4 to 0.9 when half of the number of families was used to estimate effects and the other half for prediction. Posterior probabilities of SNPs being associated with coat colour were high for regions that are known to contain loci for this trait. The prediction of phenotypes using large samples, high-density SNP data, and appropriate statistical methodology is feasible and can be applied in human medicine, forensics, or artificial selection programs. Public Library of Science 2008-10-24 /pmc/articles/PMC2565502/ /pubmed/18949033 http://dx.doi.org/10.1371/journal.pgen.1000231 Text en Lee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Sang Hong
van der Werf, Julius H. J.
Hayes, Ben J.
Goddard, Michael E.
Visscher, Peter M.
Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title_full Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title_fullStr Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title_full_unstemmed Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title_short Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data
title_sort predicting unobserved phenotypes for complex traits from whole-genome snp data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565502/
https://www.ncbi.nlm.nih.gov/pubmed/18949033
http://dx.doi.org/10.1371/journal.pgen.1000231
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