Epistasis and destabilizing mutations shape gene expression variability in humans via distinct modes of action

Increasing evidence shows that, like phenotypic mean, phenotypic variance is also genetically determined, but the underlying mechanisms of genetic control over the variance remain obscure. Here, we conducted variance-association mapping analyses to identify expression variability QTLs (evQTLs), i.e., genomic loci associated with gene expression variance, in humans. We discovered that common genetic variations may contribute to increasing gene expression variability via two distinct modes of action--epistasis and destabilization. Specifically, the epistasis model explains a quarter of the identified evQTLs, of which the formation is attributed to the presence of \"third-party\" eQTLs that inf