Gene-gene and gene-environment interactions detected by transcriptome sequence analysis in twins

Alfonso Buil (Lead / Corresponding author), Andrew Anand Brown, Tuuli Lappalainen, Ana Viñuela, Matthew N Davies, Hou-Feng Zheng, J Brent Richards, Daniel Glass, Kerrin S Small, Richard Durbin, Timothy D Spector, Emmanouil T Dermitzakis (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)


Understanding the genetic architecture of gene expression is an intermediate step in understanding the genetic architecture of complex diseases. RNA sequencing technologies have improved the quantification of gene expression and allow measurement of allele-specific expression (ASE). 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 thus far. In this study, we take advantage of a sample of twins to measure the relative contributions of genetic and environmental effects to ASE, and we find substantial effects from gene × gene (G×G) and gene × environment (G×E) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but where the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants.

Original languageEnglish
Pages (from-to)88-91
Number of pages4
JournalNature Genetics
Issue number1
Early online date1 Dec 2014
Publication statusPublished - Jan 2015


  • Alleles
  • Base Sequence
  • Epistasis, Genetic/genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation/genetics
  • Gene Frequency
  • Gene-Environment Interaction
  • Genetic Variation
  • Haplotypes/genetics
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • RNA, Messenger/biosynthesis
  • Sequence Analysis, RNA
  • Transcriptome
  • Twins, Dizygotic/genetics
  • Twins, Monozygotic/genetics


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