An integrative approach for the genetic analysis of complex traits: combining mutant phenotype and gene expression data identified novel genes impacting yeast replicative lifespan

Consistent with the model we proposed, we found that many of the peripheral genes are linked to one or more master regulators, and many of the master regulators are correlated with several peripheral genes.

Furthermore, the master regulators are linked to sets of core genes with strong overlap, covering a broad spectrum of mechanisms known to be important for aging. Our study provides support for the existence of the three-layered structure of the gene regulatory networks underlying complex traits and suggests practical approaches to identify the master regulators.