Identification and validation of risk loci for osteochondrosis in standardbreds

Annette M. McCoy, Samantha K. Beeson, Rebecca K. Splan, Sigrid Lykkjen, Sarah L. Ralston, James R Mickelson, Molly E McCue

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background: Osteochondrosis (OC), simply defined as a failure of endochondral ossification, is a complex disease with both genetic and environmental risk factors that is commonly diagnosed in young horses, as well as other domestic species. Although up to 50% of the risk for developing OC is reportedly inherited, specific genes and alleles underlying risk are thus far completely unknown. Regions of the genome identified as associated with OC vary across studies in different populations of horses. In this study, we used a cohort of Standardbred horses from the U.S. (n = 182) specifically selected for a shared early environment (to reduce confounding factors) to identify regions of the genome associated with tarsal OC. Subsequently, putative risk variants within these regions were evaluated in both the discovery population and an independently sampled validation population of Norwegian Standardbreds (n = 139) with tarsal OC. Results: After genome-wide association analysis of imputed data with information from >200,000 single nucleotide polymorphisms, two regions on equine chromosome 14 were associated with OC in the discovery cohort. Variant discovery in these and 30 additional regions of interest (including 11 from other published studies) was performed via whole-genome sequencing. 240 putative risk variants from 10 chromosomes were subsequently genotyped in both the discovery and validation cohorts. After correction for population structure, gait (trot or pace) and sex, the variants most highly associated with OC status in both populations were located within the chromosome 14 regions of association. Conclusions: The association of putative risk alleles from within the same regions with disease status in two independent populations of Standardbreds suggest that these are true risk loci in this breed, although population-specific risk factors may still exist. Evaluation of these loci in other populations will help determine if they are specific to the Standardbred breed, or to tarsal OC or are universal risk loci for OC. Further work is needed to identify the specific variants underlying OC risk within these loci. This is the first step towards the long-term goal of constructing a genetic risk model for OC that allows for genetic testing and quantification of risk in individuals.

Original languageEnglish (US)
Article number41
JournalBMC Genomics
Issue number1
StatePublished - Jan 12 2016

Bibliographical note

Funding Information:
We are grateful to Professors Nils Ivar Dolvik and Knut Røed for providing data related to the validation cohort used in this study. Special thanks to the owners and farm veterinarians involved with all included horses. This study received support from the United States Equestrian Federation, Inc., Morris Animal Foundation (D15EQ-813), the University of Minnesota Equine Center/ Minnesota Racing Commission (all to AMM and MEM), the United States Department of Agriculture (2008-35205-18766) and the Minnesota Agricultural Experiment Station (AES0063049) (to JRM). AMM was funded by an institutional NIH Training Grant (University of Minnesota; T32 OD010993) and a Doctoral Dissertation Fellowship (University of Minnesota). Partial funding for MEM was provided by NIH NIAMS 1K08AR055713-01A2.

Publisher Copyright:
© 2016 McCoy et al.


  • Cartilage
  • Developmental orthopedic disease
  • Genetic risk
  • Genome-wide association analysis
  • Horse


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