RT Journal Article SR Electronic T1 Transcriptome Sequencing Reveals Widespread Gene-Gene and Gene-Environment Interactions JF bioRxiv FD Cold Spring Harbor Laboratory SP 010546 DO 10.1101/010546 A1 Alfonso Buil A1 Andrew A. Brown A1 Tuuli Lappalainen A1 Ana ViƱuela A1 Matthew N. Davies A1 H. F. Zheng A1 J. B. Richards A1 Kerrin S. Small A1 Richard Durbin A1 Timothy D. Spector A1 Emmanouil T. Dermitzakis YR 2014 UL http://biorxiv.org/content/early/2014/10/27/010546.abstract 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.