Heritability of Recurrent Exertional Rhabdomyolyis in Thoroughbred and Standardbred Racehorses

Recurrent exertional rhabdomyolysis (RER) in Thoroughbred (TB) and Standardbred (STDB) racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise.  The objective was to evaluate the importance of genetic factors in RER by estimating heritability in cohorts of unrelated TB and STDB racehorses.  RER cases were defined as horses with a history of one or more episodes of ER and controls were defined as individuals without documented episodes of ER. 491 TB and 196 STDB were genotyped with the 54,602 or 65,153 single nucleotide polymorphism (SNP) genotyping arrays. Heritability was calculated from genome-wide SNP data using the software packages Genome-wide Complex Trait Analysis (GCTA) and Linkage Disequilibrium Adjusted Kinships (LDAK). GCTA calculates heritability using a mixed linear model with a standardized genetic relationship matrix (GRM). LDAK adjusts the GRM by assigning calculated weights to SNPs based on blocks of linkage disequilibrium. GCTA estimated heritability of RER in TB and STDB to be approximately 0.34 (sd 0.11) and 0.44 (sd 0.29), respectively, after adjusting for disease prevalence and gender. The weighted GRM increased the heritability estimate to 0.47 (sd 0.13) and decreased the estimate to 0.39 (sd 0.26) for the TB and STBD data, respectively. Thus, between 34-47% and 39-44% of the variance in RER susceptibility in TB and STBD racehorses can be explained by the SNPs present on the current genotyping arrays, indicating that RER is moderately heritable. This data provides further rationale for the investigation of genetic mutations associated with RER susceptibility.