Cercospora zeina causes grey leaf spot (GLS), a yield-limiting disease on maize. The main objective of this study was to exploit maize gene expression data to dissect the quantitative disease response to C. zeina infection. The project addresses the hypothesis that there is an underlying DNA polymorphism that gives rise to a change in gene expression, which in turn affects GLS disease severity. Genomic and functional annotation of the reporters on an Agilent 44K maize microarray was carried out. This microarray was used for global gene expression profiling of earleaf samples collected from 100 recombinant inbred sub-tropical maize lines exposed in the field to C. zeina. Gene expression profiles together with GLS severity scores were used in a weighted gene co-expression network analysis to identify co-expression modules associated with disease severity. Quantitative trait locus (QTL) mapping for GLS severity was combined with expression QTL (eQTL) analyses to investigate the molecular basis of the quantitative response to GLS. An Eqtl data analysis pipeline was developed in Galaxy. The overlap of phenotypic QTLs with cis- and trans-eQTLs revealed putative causal candidate genes and potential mechanisms responsible for the QTLs, respectively. Regulatory network models were constructed for trans-eQTL hotspots coinciding with phenotypic QTLs. A genetic basis for coordinated expression responses to GLS disease was identified. For the susceptible response, the results lead to the hypothesis that a calmodulin-related protein with a cis-eQTL acts as a global regulator of various pathogenesis-related proteins that are activated too late after infection started. For the resistant response, it is hypothesised that a serine threonineprotein kinase with a cis-eQTL acts as a post-translational global regulator regulating phosphatases and kinases involved in activation of defense gene expression. The outcomes of this study were: i) the development of a systems genetics strategy and ii) several hypotheses of maize transcriptional responses to C. zeina which need to be validated with further studies. These results extend the current knowledge of GLS resistance and could aid in the improvement of maize varieties.