PT  - JOURNAL ARTICLE
AU  - Alfonso Buil
AU  - Andrew A. Brown
AU  - Tuuli Lappalainen
AU  - Ana Viñuela
AU  - Matthew N. Davies
AU  - H. F. Zheng
AU  - J. B. Richards
AU  - Kerrin S. Small
AU  - Richard Durbin
AU  - Timothy D. Spector
AU  - Emmanouil T. Dermitzakis
TI  - Transcriptome Sequencing Reveals Widespread Gene-Gene and Gene-Environment Interactions
AID  - 10.1101/010546
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 010546
4099  - http://biorxiv.org/content/early/2014/10/27/010546.short
4100  - http://biorxiv.org/content/early/2014/10/27/010546.full
AB  - Understanding the genetic architecture of gene expression is an intermediate step to understand the genetic architecture of complex diseases. RNA-seq technologies have improved the quantification of gene expression and allow to measure allelic specific expression (ASE)1-3. ASE is hypothesized to result from the direct effect of cis regulatory variants, but a proper estimation of the causes of ASE has not been performed to date. In this study we take advantage of a sample of twins to measure the relative contribution of genetic and environmental effects on ASE and we found substantial effects of gene x gene (GxG) and gene x environment (GxE) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants. We uncover large GxG and GxE effects on gene expression and likely complex phenotypes that currently remain elusive.