Identification of Genomic Loci Associated with Rhodococcus equi Susceptibility in Foals

Pneumonia caused by Rhodococcus equi is an important cause of disease and death in foals.    Although factors related to the agent and environment are known to contribute to the incidence of this disease, genomic factors are ill-defined.  We performed independent SNP- and CNV-based GWAS to identify genomic loci associated with R. equi pneumonia.  Foals at a large Quarter Horse breeding farm were categorized in 3 groups: 1) foals without either clinical signs or thoracic ultrasonographic evidence of pneumonia (healthy controls [N = 49]); 2) foals with ultrasonographic evidence of pulmonary lesions that never developed clinical signs of pneumonia (subclinical foals [N =156]); and, 3) foals with pulmonary lesions and clinical signs of pneumonia from which R. equi was isolated (pneumonic foals [N = 43]).  From each group, 24 foals were selected randomly for SNP genotyping using the equine 70K SNP array and CNV genotyping using a high-density exome array.  The SNP-based GWAS identified a region on chromosome 26 that was moderately (P = 5.54 x 10^-6) associated with R. equi pneumonia when comparing clinical and subclinical foals.  A joint analysis using 176 additional foals and results of PCR for this locus revealed a 4-fold increase in odds of disease for the homozygous major allele (P = 0.0006). The locus contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2), which is involved in neutrophil function.  No associations were identified in the CNV-based GWAS.  Collectively, these results identify TRPM2 as a locus associated with R. equi pneumonia in foals.