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Genetic interactions affecting human gene expression identified by variance association mapping

Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance qu...

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Autores principales: Brown, Andrew Anand, Buil, Alfonso, Viñuela, Ana, Lappalainen, Tuuli, Zheng, Hou-Feng, Richards, J Brent, Small, Kerrin S, Spector, Timothy D, Dermitzakis, Emmanouil T, Durbin, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017648/
https://www.ncbi.nlm.nih.gov/pubmed/24771767
http://dx.doi.org/10.7554/eLife.01381
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author Brown, Andrew Anand
Buil, Alfonso
Viñuela, Ana
Lappalainen, Tuuli
Zheng, Hou-Feng
Richards, J Brent
Small, Kerrin S
Spector, Timothy D
Dermitzakis, Emmanouil T
Durbin, Richard
author_facet Brown, Andrew Anand
Buil, Alfonso
Viñuela, Ana
Lappalainen, Tuuli
Zheng, Hou-Feng
Richards, J Brent
Small, Kerrin S
Spector, Timothy D
Dermitzakis, Emmanouil T
Durbin, Richard
author_sort Brown, Andrew Anand
collection PubMed
description Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits. DOI: http://dx.doi.org/10.7554/eLife.01381.001
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spelling pubmed-40176482014-05-22 Genetic interactions affecting human gene expression identified by variance association mapping Brown, Andrew Anand Buil, Alfonso Viñuela, Ana Lappalainen, Tuuli Zheng, Hou-Feng Richards, J Brent Small, Kerrin S Spector, Timothy D Dermitzakis, Emmanouil T Durbin, Richard eLife Genes and Chromosomes Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits. DOI: http://dx.doi.org/10.7554/eLife.01381.001 eLife Sciences Publications, Ltd 2014-04-25 /pmc/articles/PMC4017648/ /pubmed/24771767 http://dx.doi.org/10.7554/eLife.01381 Text en Copyright © 2014, Brown et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genes and Chromosomes
Brown, Andrew Anand
Buil, Alfonso
Viñuela, Ana
Lappalainen, Tuuli
Zheng, Hou-Feng
Richards, J Brent
Small, Kerrin S
Spector, Timothy D
Dermitzakis, Emmanouil T
Durbin, Richard
Genetic interactions affecting human gene expression identified by variance association mapping
title Genetic interactions affecting human gene expression identified by variance association mapping
title_full Genetic interactions affecting human gene expression identified by variance association mapping
title_fullStr Genetic interactions affecting human gene expression identified by variance association mapping
title_full_unstemmed Genetic interactions affecting human gene expression identified by variance association mapping
title_short Genetic interactions affecting human gene expression identified by variance association mapping
title_sort genetic interactions affecting human gene expression identified by variance association mapping
topic Genes and Chromosomes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017648/
https://www.ncbi.nlm.nih.gov/pubmed/24771767
http://dx.doi.org/10.7554/eLife.01381
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