Genetic interactions affecting human gene expression identified by variance association mapping
- Wellcome Trust Sanger Institute, United Kingdom
- University of Geneva, Switzerland
- King's College London, United Kingdom
- McGill University, Canada
- The Wellcome Trust Sanger Institute, United Kingdom
Abstract
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.
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Ethics
Human subjects: This project was approved by the ethics committee at St Thomas' Hospital London, where all the biopsies were carried out. Volunteers gave informed consent and signed an approved consent form prior to the biopsy procedure. Volunteers were supplied with an appropriate detailed information sheet regarding the research project and biopsy procedure by post prior to attending for the biopsy. The St. Thomas' Research Ethics Committee (REC) approved on 20th September 2007 the protocol for dissemination of data, including DNA, with the REC reference number RE04/015. On 12th of March of 2008, the St Thomas' REC confirmed this approval extends to expression data.
Copyright
© 2014, Brown et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Genetic interactions affecting human gene expression identified by variance association mapping
eLife 3:e01381.
https://doi.org/10.7554/eLife.01381
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