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Genetic interactions affecting human gene expression identified by variance association mapping

Lookup NU author(s): Dr Ana ViƱuelaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Brown AA, Buil A, Vinuela A, Lappalainen T, Zheng H-F, Richards JB, Small KS, Spector TD, Dermitzakis ET, Durbin R

Publication type: Article

Publication status: Published

Journal: eLife

Year: 2014

Volume: 2014

Issue: 3

Online publication date: 25/04/2014

Acceptance date: 13/03/2014

Date deposited: 29/06/2020

ISSN (electronic): 2050-084X

Publisher: eLife Sciences Publications Ltd


DOI: 10.7554/eLife.01381

PubMed id: 24771767


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