shows that *cis*-eQTLs primarily cause variation in transcription factor (TF) binding to gene regulatory DNA elements, which then causes changes in histone modifications, DNA methylation and mRNA expression of nearby genes; *trans*-eQTLs in turn can usually be attributed to coding variants in regulatory genes or *cis*-eQTLs of such genes [@albert2015role].

Taken together, these results motivate and justify a systems biological view of quantitative genetics (“systems genetics”), where it is hypothesized that genetic variation, together with environmental perturbations, affects the status of molecular networks of interacting genes, proteins and metabolites; these networks act within and across different tissues and collectively control physiological phenotypes [@williams2006expression; @kadarmideen2006genetical; @rockman2008reverse; @schadt2009; @schadt2012new; @civelek2014systems; @bjorkegren2015genome]. Studying the impact of genetic variation on gene regulation networks is of crucial importance in understanding the fundamental biological mechanisms by which genetic variation causes variation in phenotypes [@chen2008], and is expected to lead to the discovery of novel disease biomarkers and drug targets in human and veterinary medicine [@schadt2009b]. Since direct experimental mapping of genetic, protein–protein or protein–DNA interactions is an immensely challenging task, further exacerbated by the cell-type specific and dynamic nature of these interactions [@walhout2006unraveling], comprehensive, experimentally verified molecular networks will not become available for multi-cellular organisms in 