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Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis

BACKGROUND: Multi-marker methods, which fit all markers simultaneously, were originally tailored for genomic selection purposes, but have proven to be useful also in association analyses, especially the so-called BayesC Bayesian methods. In a recent study, BayesD extended BayesC towards accounting f...

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Autores principales: Bennewitz, Jörn, Edel, Christian, Fries, Ruedi, Meuwissen, Theo H. E., Wellmann, Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237573/
https://www.ncbi.nlm.nih.gov/pubmed/28088170
http://dx.doi.org/10.1186/s12711-017-0284-7
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author Bennewitz, Jörn
Edel, Christian
Fries, Ruedi
Meuwissen, Theo H. E.
Wellmann, Robin
author_facet Bennewitz, Jörn
Edel, Christian
Fries, Ruedi
Meuwissen, Theo H. E.
Wellmann, Robin
author_sort Bennewitz, Jörn
collection PubMed
description BACKGROUND: Multi-marker methods, which fit all markers simultaneously, were originally tailored for genomic selection purposes, but have proven to be useful also in association analyses, especially the so-called BayesC Bayesian methods. In a recent study, BayesD extended BayesC towards accounting for dominance effects and improved prediction accuracy and persistence in genomic selection. The current study investigated the power and precision of BayesC and BayesD in genome-wide association studies by means of stochastic simulations and applied these methods to a dairy cattle dataset. METHODS: The simulation protocol was designed to mimic the genetic architecture of quantitative traits as realistically as possible. Special emphasis was put on the joint distribution of the additive and dominance effects of causative mutations. Additive marker effects were estimated by BayesC and additive and dominance effects by BayesD. The dependencies between additive and dominance effects were modelled in BayesD by choosing appropriate priors. A sliding-window approach was used. For each window, the R. Fernando window posterior probability of association was calculated and this was used for inference purpose. The power to map segregating causal effects and the mapping precision were assessed for various marker densities up to full sequence information and various window sizes. RESULTS: Power to map a QTL increased with higher marker densities and larger window sizes. This held true for both methods. Method BayesD had improved power compared to BayesC. The increase in power was between −2 and 8% for causative genes that explained more than 2.5% of the genetic variance. In addition, inspection of the estimates of genomic window dominance variance allowed for inference about the magnitude of dominance at significant associations, which remains hidden in BayesC analysis. Mapping precision was not substantially improved by BayesD. CONCLUSIONS: BayesD improved power, but precision only slightly. Application of BayesD needs large datasets with genotypes and own performance records as phenotypes. Given the current efforts to establish cow reference populations in dairy cattle genomic selection schemes, such datasets are expected to be soon available, which will enable the application of BayesD for association mapping and genomic prediction purposes.
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spelling pubmed-52375732017-01-18 Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis Bennewitz, Jörn Edel, Christian Fries, Ruedi Meuwissen, Theo H. E. Wellmann, Robin Genet Sel Evol Research Article BACKGROUND: Multi-marker methods, which fit all markers simultaneously, were originally tailored for genomic selection purposes, but have proven to be useful also in association analyses, especially the so-called BayesC Bayesian methods. In a recent study, BayesD extended BayesC towards accounting for dominance effects and improved prediction accuracy and persistence in genomic selection. The current study investigated the power and precision of BayesC and BayesD in genome-wide association studies by means of stochastic simulations and applied these methods to a dairy cattle dataset. METHODS: The simulation protocol was designed to mimic the genetic architecture of quantitative traits as realistically as possible. Special emphasis was put on the joint distribution of the additive and dominance effects of causative mutations. Additive marker effects were estimated by BayesC and additive and dominance effects by BayesD. The dependencies between additive and dominance effects were modelled in BayesD by choosing appropriate priors. A sliding-window approach was used. For each window, the R. Fernando window posterior probability of association was calculated and this was used for inference purpose. The power to map segregating causal effects and the mapping precision were assessed for various marker densities up to full sequence information and various window sizes. RESULTS: Power to map a QTL increased with higher marker densities and larger window sizes. This held true for both methods. Method BayesD had improved power compared to BayesC. The increase in power was between −2 and 8% for causative genes that explained more than 2.5% of the genetic variance. In addition, inspection of the estimates of genomic window dominance variance allowed for inference about the magnitude of dominance at significant associations, which remains hidden in BayesC analysis. Mapping precision was not substantially improved by BayesD. CONCLUSIONS: BayesD improved power, but precision only slightly. Application of BayesD needs large datasets with genotypes and own performance records as phenotypes. Given the current efforts to establish cow reference populations in dairy cattle genomic selection schemes, such datasets are expected to be soon available, which will enable the application of BayesD for association mapping and genomic prediction purposes. BioMed Central 2017-01-14 /pmc/articles/PMC5237573/ /pubmed/28088170 http://dx.doi.org/10.1186/s12711-017-0284-7 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bennewitz, Jörn
Edel, Christian
Fries, Ruedi
Meuwissen, Theo H. E.
Wellmann, Robin
Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title_full Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title_fullStr Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title_full_unstemmed Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title_short Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
title_sort application of a bayesian dominance model improves power in quantitative trait genome-wide association analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237573/
https://www.ncbi.nlm.nih.gov/pubmed/28088170
http://dx.doi.org/10.1186/s12711-017-0284-7
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