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

ABSTRACT: Increasing evidence shows that phenotypic variance is 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 variants may contribute to increasing gene expression variance via two distinct modes of action—epistasis and destabilization. Specifically, epistasis explains a quarter of the identified evQTLs, of which the formation is attributed to the presence of ‘third-party’ eQTLs that influence the gene expression mean in a fraction, rather than the entire set, of sampled individuals. On the other hand, the destabilization model exp

SUBMITTER: Yang E 

PROVIDER: S-EPMC6078589 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature