Biological organisms are complex systems that are composed of pleiotropic functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. However, due to the many pleiotropic interactions present in cells, perturbing one set of phenotypes, such as cell walls may well affect other core functions, including plant-microbe interactions. We are using data derived from the re-sequenced genomes from over 1000 different Populus trichocarpa genotypes in combination with transcriptomics, metabolomics and phenomics data across this population in order to better understand the molecular interactions involved in recalcitrance. The resulting Genome Wide Association Study networks, integrated with SNP correlation and co-expression networks, are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance and to make hypotheses about the other phenotypes that may be affected