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Disease arises from the interaction of two genomes, host and pathogen genomes. To highlight these genomic interactions, Soltis et al.performed genome-wide association (GWA) based on genetic variation in the pathogen...In plant–pathogen relations, disease symptoms arise from the interaction of the host and pathogen genomes. Host–pathogen functional gene interactions are well described, whereas little is known about how the pathogen genetic variation modulates both organisms’ transcriptomes. To model and generate hypotheses on a generalist pathogen control of gene expression regulation, we used the Arabidopsis thaliana–Botrytis cinereapathosystem and the genetic diversity of a collection of 96 B. cinereaisolates. We performed expression-based genome-wide association (eGWA) for each of 23,947 measurable transcripts in Arabidopsis(host), and 9267 measurable transcripts in B. cinerea(pathogen). Unlike other eGWA studies, we detected a relative absence of locally acting expression quantitative trait loci (cis-eQTL), partly caused by structural variants and allelic heterogeneity hindering their identification. This study identified several distantly acting trans-eQTL linked to eQTL hotspots dispersed across Botrytisgenome that altered only Botrytistranscripts, only Arabidopsistranscripts, or transcripts from both species. Gene membership in the trans-eQTL hotspots suggests links between gene expression regulation and both known and novel virulence mechanisms in this pathosystem. Genes annotated to these hotspots provide potential targets for blocking manipulation of the host response by this ubiquitous generalist necrotrophic pathogen.