One of the persistent problems in biology is understanding how genetic variation contributes to phenotypic variation. Associations at many levels have been reported, and yet causal inference has remained elusive. We propose to rely on the knowledge of causal relationships established by molecular biology approaches. The existing molecular knowledge forms a firm backbone upon which hypotheses connecting genetic variation, transcriptional variation and phenotypic variation can be built. The sex determination pathway is a well-established molecular network, with the Yp genes as the most downstream target. Our analyses reveal that genetic variation in expression for genes known to be upstream in the pathway explains variation in downstream targets. Relationships differ between the two sexes, and each Yp has a distinct transcriptional pattern. Yp expression is significantly negatively correlated with longevity, an important life history trait, for both males and females.