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GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data

Intermediate phenotypes such as gene expression values can be used to elucidate the mechanisms by which genetic variation causes phenotypic variation, but jointly analyzing such heterogeneous data are far from trivial. Here we extend a so-called mediation model to handle the confounding effects of g...

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Detalles Bibliográficos
Autores principales: Sasaki, Eriko, Frommlet, Florian, Nordborg, Magnus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118313/
https://www.ncbi.nlm.nih.gov/pubmed/30068524
http://dx.doi.org/10.1534/g3.118.200571
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author Sasaki, Eriko
Frommlet, Florian
Nordborg, Magnus
author_facet Sasaki, Eriko
Frommlet, Florian
Nordborg, Magnus
author_sort Sasaki, Eriko
collection PubMed
description Intermediate phenotypes such as gene expression values can be used to elucidate the mechanisms by which genetic variation causes phenotypic variation, but jointly analyzing such heterogeneous data are far from trivial. Here we extend a so-called mediation model to handle the confounding effects of genetic background, and use it to analyze flowering time variation in Arabidopsis thaliana, focusing in particular on the central role played by the key regulator FLOWERING TIME LOCUS C (FLC). FLC polymorphism and FLC expression are both strongly correlated with flowering time variation, but the effect of the former is only partly mediated through the latter. Furthermore, the latter also reflects genetic background effects. We demonstrate that it is possible to partition these effects, shedding light on the complex regulatory network that underlies flowering time variation.
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spelling pubmed-61183132018-09-04 GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data Sasaki, Eriko Frommlet, Florian Nordborg, Magnus G3 (Bethesda) Investigations Intermediate phenotypes such as gene expression values can be used to elucidate the mechanisms by which genetic variation causes phenotypic variation, but jointly analyzing such heterogeneous data are far from trivial. Here we extend a so-called mediation model to handle the confounding effects of genetic background, and use it to analyze flowering time variation in Arabidopsis thaliana, focusing in particular on the central role played by the key regulator FLOWERING TIME LOCUS C (FLC). FLC polymorphism and FLC expression are both strongly correlated with flowering time variation, but the effect of the former is only partly mediated through the latter. Furthermore, the latter also reflects genetic background effects. We demonstrate that it is possible to partition these effects, shedding light on the complex regulatory network that underlies flowering time variation. Genetics Society of America 2018-08-01 /pmc/articles/PMC6118313/ /pubmed/30068524 http://dx.doi.org/10.1534/g3.118.200571 Text en Copyright © 2018 Sasaki et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article 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 the original work is properly cited.
spellingShingle Investigations
Sasaki, Eriko
Frommlet, Florian
Nordborg, Magnus
GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title_full GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title_fullStr GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title_full_unstemmed GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title_short GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data
title_sort gwas with heterogeneous data: estimating the fraction of phenotypic variation mediated by gene expression data
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118313/
https://www.ncbi.nlm.nih.gov/pubmed/30068524
http://dx.doi.org/10.1534/g3.118.200571
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