Comparison of GWA statistical methods for traits under different genetic structures: A simulation study

Detalhes bibliográficos
Autor(a) principal: Garcia, Baltasar Fernandes [UNESP]
Data de Publicação: 2020
Outros Autores: Melo, Thaise Pinto de [UNESP], Neves, Haroldo Henrique de Rezende, Carvalheiro, Roberto [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.livsci.2020.104213
http://hdl.handle.net/11449/199254
Resumo: Several methods have been used to perform genome wide association (GWA) studies, aiming to map quantitative trait loci (QTL) and candidate variants. The single-step genomic best linear unbiased prediction (ssGBLUP) method is one alternative to perform GWA, which allows the simultaneous use of genotypic, pedigree and phenotypic information. Bayesian multiple regression models have also been used to perform GWA, allowing specifying different priori distribution for the molecular marker effects. The aim of the present study was to evaluate, through simulation, the performance of different methods in the identification of QTLs for polygenic and major gene traits, under different heritabilities when only relatively few animals were genotyped. We also investigated the consequence of considering the agreement among results from different methods as a strategy to decrease errors associated with false positives in QTL mapping. For polygenic scenarios, results showed low power to detect QTL, irrespective of the method, and the use of phenotypes from non-genotyped animals slightly helped QTL detection of ssGBLUP and weighted ssGBLUP (wssGBLUP). For scenarios with major gene effects, there was greater power in QTL detection, with a slight superiority of Bayes C over the other methods. The inclusion of additional phenotypic information (from non-genotyped animals) harmed the performance of wssGBLUP in the presence of major QTL. When only consensus regions identified by different methods were considered as evidence of QTL, the percentage of top windows containing a true QTL tended to increase with the number of methods that identified a top window, for all scenarios. However, an important proportion of true QTL were identified only by a single or few methods. Despite the small differences among methods in the QTL detection, for polygenic traits, the ssGBLUP and wssGBLUP methods seemed to show better results in comparison to the other methods mainly in the low heritability scenario. For traits with major gene effects, the Bayes C method is expected to present better results, compared to the other methods evaluated, given a limited number of genotyped animals. The strategy to use agreement of GWA results among methods to map QTL helps to reduce false positives but comes at a cost of missing important QTL, irrespective of the genetic structure of the trait.
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spelling Comparison of GWA statistical methods for traits under different genetic structures: A simulation studyBayesian methodsGWAQTL mappingweighted single-step GBLUPSeveral methods have been used to perform genome wide association (GWA) studies, aiming to map quantitative trait loci (QTL) and candidate variants. The single-step genomic best linear unbiased prediction (ssGBLUP) method is one alternative to perform GWA, which allows the simultaneous use of genotypic, pedigree and phenotypic information. Bayesian multiple regression models have also been used to perform GWA, allowing specifying different priori distribution for the molecular marker effects. The aim of the present study was to evaluate, through simulation, the performance of different methods in the identification of QTLs for polygenic and major gene traits, under different heritabilities when only relatively few animals were genotyped. We also investigated the consequence of considering the agreement among results from different methods as a strategy to decrease errors associated with false positives in QTL mapping. For polygenic scenarios, results showed low power to detect QTL, irrespective of the method, and the use of phenotypes from non-genotyped animals slightly helped QTL detection of ssGBLUP and weighted ssGBLUP (wssGBLUP). For scenarios with major gene effects, there was greater power in QTL detection, with a slight superiority of Bayes C over the other methods. The inclusion of additional phenotypic information (from non-genotyped animals) harmed the performance of wssGBLUP in the presence of major QTL. When only consensus regions identified by different methods were considered as evidence of QTL, the percentage of top windows containing a true QTL tended to increase with the number of methods that identified a top window, for all scenarios. However, an important proportion of true QTL were identified only by a single or few methods. Despite the small differences among methods in the QTL detection, for polygenic traits, the ssGBLUP and wssGBLUP methods seemed to show better results in comparison to the other methods mainly in the low heritability scenario. For traits with major gene effects, the Bayes C method is expected to present better results, compared to the other methods evaluated, given a limited number of genotyped animals. The strategy to use agreement of GWA results among methods to map QTL helps to reduce false positives but comes at a cost of missing important QTL, irrespective of the genetic structure of the trait.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Department of Animal Science School of Agricultural and Veterinary Sciences São Paulo State University (UNESP) Via de Acesso Prof. Paulo Donato CastellaneGenSys Consultores Associados S/C LtdaNational Council for Science and Technological DevelopmentDepartment of Animal Science School of Agricultural and Veterinary Sciences São Paulo State University (UNESP) Via de Acesso Prof. Paulo Donato CastellaneCAPES: 2013Universidade Estadual Paulista (Unesp)GenSys Consultores Associados S/C LtdaNational Council for Science and Technological DevelopmentGarcia, Baltasar Fernandes [UNESP]Melo, Thaise Pinto de [UNESP]Neves, Haroldo Henrique de RezendeCarvalheiro, Roberto [UNESP]2020-12-12T01:34:55Z2020-12-12T01:34:55Z2020-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.livsci.2020.104213Livestock Science, v. 241.1871-1413http://hdl.handle.net/11449/19925410.1016/j.livsci.2020.1042132-s2.0-85089410182Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLivestock Scienceinfo:eu-repo/semantics/openAccess2021-10-23T05:43:37Zoai:repositorio.unesp.br:11449/199254Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T05:43:37Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
title Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
spellingShingle Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
Garcia, Baltasar Fernandes [UNESP]
Bayesian methods
GWA
QTL mapping
weighted single-step GBLUP
title_short Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
title_full Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
title_fullStr Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
title_full_unstemmed Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
title_sort Comparison of GWA statistical methods for traits under different genetic structures: A simulation study
author Garcia, Baltasar Fernandes [UNESP]
author_facet Garcia, Baltasar Fernandes [UNESP]
Melo, Thaise Pinto de [UNESP]
Neves, Haroldo Henrique de Rezende
Carvalheiro, Roberto [UNESP]
author_role author
author2 Melo, Thaise Pinto de [UNESP]
Neves, Haroldo Henrique de Rezende
Carvalheiro, Roberto [UNESP]
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
GenSys Consultores Associados S/C Ltda
National Council for Science and Technological Development
dc.contributor.author.fl_str_mv Garcia, Baltasar Fernandes [UNESP]
Melo, Thaise Pinto de [UNESP]
Neves, Haroldo Henrique de Rezende
Carvalheiro, Roberto [UNESP]
dc.subject.por.fl_str_mv Bayesian methods
GWA
QTL mapping
weighted single-step GBLUP
topic Bayesian methods
GWA
QTL mapping
weighted single-step GBLUP
description Several methods have been used to perform genome wide association (GWA) studies, aiming to map quantitative trait loci (QTL) and candidate variants. The single-step genomic best linear unbiased prediction (ssGBLUP) method is one alternative to perform GWA, which allows the simultaneous use of genotypic, pedigree and phenotypic information. Bayesian multiple regression models have also been used to perform GWA, allowing specifying different priori distribution for the molecular marker effects. The aim of the present study was to evaluate, through simulation, the performance of different methods in the identification of QTLs for polygenic and major gene traits, under different heritabilities when only relatively few animals were genotyped. We also investigated the consequence of considering the agreement among results from different methods as a strategy to decrease errors associated with false positives in QTL mapping. For polygenic scenarios, results showed low power to detect QTL, irrespective of the method, and the use of phenotypes from non-genotyped animals slightly helped QTL detection of ssGBLUP and weighted ssGBLUP (wssGBLUP). For scenarios with major gene effects, there was greater power in QTL detection, with a slight superiority of Bayes C over the other methods. The inclusion of additional phenotypic information (from non-genotyped animals) harmed the performance of wssGBLUP in the presence of major QTL. When only consensus regions identified by different methods were considered as evidence of QTL, the percentage of top windows containing a true QTL tended to increase with the number of methods that identified a top window, for all scenarios. However, an important proportion of true QTL were identified only by a single or few methods. Despite the small differences among methods in the QTL detection, for polygenic traits, the ssGBLUP and wssGBLUP methods seemed to show better results in comparison to the other methods mainly in the low heritability scenario. For traits with major gene effects, the Bayes C method is expected to present better results, compared to the other methods evaluated, given a limited number of genotyped animals. The strategy to use agreement of GWA results among methods to map QTL helps to reduce false positives but comes at a cost of missing important QTL, irrespective of the genetic structure of the trait.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-12T01:34:55Z
2020-12-12T01:34:55Z
2020-11-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.livsci.2020.104213
Livestock Science, v. 241.
1871-1413
http://hdl.handle.net/11449/199254
10.1016/j.livsci.2020.104213
2-s2.0-85089410182
url http://dx.doi.org/10.1016/j.livsci.2020.104213
http://hdl.handle.net/11449/199254
identifier_str_mv Livestock Science, v. 241.
1871-1413
10.1016/j.livsci.2020.104213
2-s2.0-85089410182
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Livestock Science
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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