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Background  Severe equine asthma, also known as recurrent airway obstruction (RAO), is a debilitating, performance limiting, obstructive respiratory condition in horses that is phenotypically similar to human asthma. Past genome wide association studies (GWAS) have not discovered coding variants associated with RAO, leading to the hypothesis that causative variant(s) underlying the signals are likely non-coding, regulatory variant(s). Regions of the genome containing variants that influence the number of expressed RNA molecules are expression quantitative trait loci (eQTLs). Variation associated with RAO that also regulates a gene’s expression in a disease relevant tissue could help identify candidate genes that influence RAO if that gene’s expression is also associated with RAO disease status.    Results  We searched for eQTLs by analyzing peripheral blood mononuclear cells (PBMCs) from two half-sib families and one unrelated cohort of 82 European Warmblood horses that were previously treated in vitro with: no stimulation (MCK), lipopolysaccharides (LPS), recombinant cyathostomin antigen (RCA), and hay-dust extract (HDE). We identified high confidence eQTLs that did not violate linear modeling assumptions and were not significant due to single outlier individuals. We identified a mean of 4347 high confidence eQTLs in four treatments of PBMCs, and discovered two  trans  regulatory hotspots regulating genes involved in related biological pathways. We corroborated previous RAO associated single nucleotide polymorphisms (SNPs), and increased the resolution of past GWAS by analyzing 1,056,195 SNPs in 361 individuals. We identified four RAO-associated SNPs that only regulate gene expression of dexamethasone-induced protein ( DEXI ), however we found no significant association between  DEXI  gene expression and presence of RAO.    Conclusions  Thousands of genetic variants regulate gene expression in PBMCs of European Warmblood horses in  cis  and  trans . Most high confidence eSNPs are significantly enriched near the transcription start sites of their target genes. Two  trans  regulatory hotspots on chromosome 11 and 13 regulate many genes involved in transmembrane cell signaling and neurological development respectively when PBMCs are treated with HDE. None of the top fifteen RAO associated SNPs strongly influence disease status through gene expression regulation.    Electronic supplementary material  The online version of this article (10.1186/s12864-018-4938-9) contains supplementary material, which is available to authorized users.

eQTL discovery and their association with severe equine asthma in European Warmblood horses