Variance heterogeneity in Saccharomyces cerevisiae expression data: trans-regulation and epistasis

PLoS One. 2013 Nov 4;8(11):e79507. doi: 10.1371/journal.pone.0079507. eCollection 2013.


Here, we describe the results from the first variance heterogeneity Genome Wide Association Study (VGWAS) on yeast expression data. Using this forward genetics approach, we show that the genetic regulation of gene-expression in the budding yeast, Saccharomyces cerevisiae, includes mechanisms that can lead to variance heterogeneity in the expression between genotypes. Additionally, we performed a mean effect association study (GWAS). Comparing the mean and variance heterogeneity analyses, we find that the mean expression level is under genetic regulation from a larger absolute number of loci but that a higher proportion of the variance controlling loci were trans-regulated. Both mean and variance regulating loci cluster in regulatory hotspots that affect a large number of phenotypes; a single variance-controlling locus, mapping close to DIA2, was found to be involved in more than 10% of the significant associations. It has been suggested in the literature that variance-heterogeneity between the genotypes might be due to genetic interactions. We therefore screened the multi-locus genotype-phenotype maps for several traits where multiple associations were found, for indications of epistasis. Several examples of two and three locus genetic interactions were found to involve variance-controlling loci, with reports from the literature corroborating the functional connections between the loci. By using a new analytical approach to re-analyze a powerful existing dataset, we are thus able to both provide novel insights to the genetic mechanisms involved in the regulation of gene-expression in budding yeast and experimentally validate epistasis as an important mechanism underlying genetic variance-heterogeneity between genotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epistasis, Genetic*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Pyrimidines / metabolism
  • Quantitative Trait Loci / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcriptome


  • Pyrimidines
  • Saccharomyces cerevisiae Proteins
  • pyrimidine

Associated data

  • GEO/GSE9376

Grant support

This study was funded by the Swedish Foundation for Strategic Research; by Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning (FORMAS); and by a EURYI Award to ÖC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.