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Meta‐analysis of genome‐wide association from genomic prediction models

Genome‐wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, o...

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Autores principales: Bernal Rubio, Y. L., Gualdrón Duarte, J. L., Bates, R. O., Ernst, C. W., Nonneman, D., Rohrer, G. A., King, A., Shackelford, S. D., Wheeler, T. L., Cantet, R. J. C., Steibel, J. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738412/
https://www.ncbi.nlm.nih.gov/pubmed/26607299
http://dx.doi.org/10.1111/age.12378
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author Bernal Rubio, Y. L.
Gualdrón Duarte, J. L.
Bates, R. O.
Ernst, C. W.
Nonneman, D.
Rohrer, G. A.
King, A.
Shackelford, S. D.
Wheeler, T. L.
Cantet, R. J. C.
Steibel, J. P.
author_facet Bernal Rubio, Y. L.
Gualdrón Duarte, J. L.
Bates, R. O.
Ernst, C. W.
Nonneman, D.
Rohrer, G. A.
King, A.
Shackelford, S. D.
Wheeler, T. L.
Cantet, R. J. C.
Steibel, J. P.
author_sort Bernal Rubio, Y. L.
collection PubMed
description Genome‐wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta‐analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal‐centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population‐level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits.
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spelling pubmed-47384122016-02-12 Meta‐analysis of genome‐wide association from genomic prediction models Bernal Rubio, Y. L. Gualdrón Duarte, J. L. Bates, R. O. Ernst, C. W. Nonneman, D. Rohrer, G. A. King, A. Shackelford, S. D. Wheeler, T. L. Cantet, R. J. C. Steibel, J. P. Anim Genet Articles Genome‐wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta‐analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal‐centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population‐level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits. John Wiley and Sons Inc. 2015-11-26 2016-02 /pmc/articles/PMC4738412/ /pubmed/26607299 http://dx.doi.org/10.1111/age.12378 Text en © 2015 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Bernal Rubio, Y. L.
Gualdrón Duarte, J. L.
Bates, R. O.
Ernst, C. W.
Nonneman, D.
Rohrer, G. A.
King, A.
Shackelford, S. D.
Wheeler, T. L.
Cantet, R. J. C.
Steibel, J. P.
Meta‐analysis of genome‐wide association from genomic prediction models
title Meta‐analysis of genome‐wide association from genomic prediction models
title_full Meta‐analysis of genome‐wide association from genomic prediction models
title_fullStr Meta‐analysis of genome‐wide association from genomic prediction models
title_full_unstemmed Meta‐analysis of genome‐wide association from genomic prediction models
title_short Meta‐analysis of genome‐wide association from genomic prediction models
title_sort meta‐analysis of genome‐wide association from genomic prediction models
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738412/
https://www.ncbi.nlm.nih.gov/pubmed/26607299
http://dx.doi.org/10.1111/age.12378
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