Gene Loci for Recurrent Exertional Rhabdomyolysis in Thoroughbreds and Standardbreds

Approximately 5-10% of Thoroughbred (TB) and 6% of Standardbred (STDB) racehorses suffer from recurrent exertional rhabdomyolysis (RER), a condition characterized by bouts of painful cramping and muscle cell damage following exercise. There is strong evidence for a genetic component conferring RER susceptibility, with gender, temperament, diet, and activity level influencing expression of the clinical phenotype; however, the specific genetic variants actually contributing to this susceptibility are unknown. We hypothesized that variants of moderate to major effect underlie RER susceptibility in TB and STDB horses and that some of these variants are shared across both breeds. The objective of this project was to identify these variants associated with RER risk. We performed genome-wide association studies (GWAS) to determine RER susceptibility loci in populations of TB (n=491) and STDB (n=196) horses. These GWAS identified 4 chromosomal loci associated with RER susceptibility: 2 in TBs, 1 in STDBs,  and one locus shared across both breeds.  These regions of interest (ROI) ranged in size from 3400kb to 8420kb. Variants in each ROI were identified using whole genome sequences from 5 RER and 5 controls in each breed. 71,018 variants were discovered within the ROIs, with an average of 3.6 variants per kb. Of the variants identified, 52.6% were within genes, and 1.5% had a putative functional effect. Variants will be prioritized based on segregation between RER and control horses as well as predicted functional effect. High-priority variants will then be used to create an assay for genotyping in the entire GWAS population.