Genetic interactions affecting human gene expression identified by variance association mapping

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

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70 Citations (Scopus)
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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.DOI:

Original languageEnglish
Article numbere01381
Pages (from-to)1-16
Number of pages16
Publication statusPublished - 25 Apr 2014


  • Biostatistics
  • Epistasis, Genetic
  • Humans
  • Multifactorial Inheritance
  • Quantitative Trait, Heritable


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