title: 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 genome-wide 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 on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility.
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Norton
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: James R
authors.initials: JR
authors.lastname: Mickelson
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Binns
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Blott
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Paul
authors.initials: P
authors.lastname: Caputo
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Cajsa M
authors.initials: CM
authors.lastname: Isgren
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Annette M
authors.initials: AM
authors.lastname: McCoy
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Alison
authors.initials: A
authors.lastname: Moore
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Piercy
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: June E
authors.initials: JE
authors.lastname: Swinburne
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin).
authors.forename: Mark
authors.initials: M
authors.lastname: Vaudin
authors.affiliation: From the Veterinary Population Medicine Department, University of Minnesota, 225 Veterinary Medical Center, 1365 Gortner Ave, St. Paul, MN 55108 (Norton and McCue); Veterinary Biomedical Sciences Department, University of Minnesota, St. Paul, MN (Mickelson); Equine Analysis Systems, LLC, Midway, KY (Binns); School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, UK (Blott); 333 SW 14th Ave, Pompano Beach, FL (Caputo); School of Veterinary Science, University of Liverpool; Philip Leverhulme Equine Hospital, University of Liverpool Leahurst Campus, Wirral, UK (Isgren); Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL (McCoy); Moore Equine Services, Cambridge, Canada (Moore); Department of Clinical Sciences and Services, The Royal Veterinary College, Hertfordshire, UK (Piercy); Animal DNA Diagnostics LTD, Cambridge, UK (Swinburne); and Animal Health Trust, Suffolk, UK (Vaudin). mccu0173@umn.edu.
authors.forename: Molly E
authors.initials: ME
authors.lastname: McCue
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D040941:Heredity; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012206:Rhabdomyolysis / Q000662:veterinary*
keywords: RER; muscle disease; tying-up