A growing body of evidence suggests that changes in gene regulatory DNA are the major genetic determinants of variation in complex phenotypes; however, the underlying genes as well as cascades of intermediate molecular events remain in most cases elusive. This work has therefore centered on elucidating the genetic architecture of complex molecular phenotypes (i.e., protein-DNA interactions, chromatin structure, and gene expression) in different model systems in order to study the molecular consequences of regulatory DNA variation. The main contributions are: i.) a genome-wide map of gene expression-associated regulatory loci in Drosophila melanogaster; ii.) novel regulatory components in the murine adipogenic gene regulatory network; iii.) an algorithm to identify biased genetic associations with epigenomic datasets; and iv.) novel insights into the intermediatemolecular consequences of regulatory DNA variation within and between humans.