Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data

Abstract

Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred 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 obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genomewide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present

Heritability of metabolic traits associated with equine metabolic syndrome in Welsh ponies and Morgan horses

“…As we have previously shown, increasing the population size would also reduce the relatively large s.e. seen with all our estimates, but would not affect the overall h 2 SNP estimate [27]. The one trait with an unadjusted P>0.05 was ACTH in the Morgans, which was also the trait that had the largest difference between the original and mean subset value.…”

Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis

“…Previous studies of RER have failed to identify a single genome‐wide significant candidate locus for RER, suggesting that multiple genes, strong environmental influences, or both are at play . The heritability of RER in TB and STD horses has been estimated at approximately 0.40 . Environmental factors such as sex, diet, fitness, and stress also have been shown to play important roles in expression of RER …”

“…The heritability of RER in TB and STD horses has been estimated at approximately 0.40 . Environmental factors such as sex, diet, fitness, and stress also have been shown to play important roles in expression of RER …”

Ethics, Genetic Technologies and Equine Sports: The Prospect of Regulation of a Modified Therapeutic Use Exemption Policy

“…Nonetheless, a significant genetic variation for risk of fracture in Thoroughbred racehorses has been identified , and the traits which are associated with athletic durability investigated Velie, Hamilton, and Wade 2016). The genetic basis of equine exertional rhabdomyolosis has also been studied (Norton et al 2016). This is in some ways analogous to the work on sickle-cell anaemia-related exertional rhabdomyolosis in humans, and will be of relevance to the welfare of endurance (Nagy, Murray, and Dyson 2014) as well as of racehorses.…”

“…Equally, genetic editing has the potential to improve equine welfare by reducing hereditary predisposition to disease and injury. There are a number of performanceaffecting equine diseases which are already known to have a hereditary basis-for example, equine exertional rhabdomyolosis (Norton et al 2016) and osteochondrosis dissecans (Naccache, Metzger, and Distl 2018). It is also possible that some injuries which occur during racing (e.g.…”