Investigation and Validation of Variants Underlying Osteochondrosis Risk in the Horse

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. Although up to 50% of the risk for developing OC is reportedly inherited, the genes/alleles underlying this risk are unknown. The aim of this study was to identify putative functional variants underlying genetic risk for OC in the horse, using Standardbreds with tarsal OC as a model population.

A genome-wide association analysis was performed in 182 Standardbred horses from a single breeding farm in the United States. Two distinct loci on equine (ECA) chromosome 14 were moderately associated with OC status in this cohort. Variant discovery was subsequently performed via whole-genome sequencing in 18 horses. Variants within the associated regions on ECA14, as well as from 9 previously published regions of association for tarsal OC, were prioritized based on predicted functional effect and segregation with OC status. 240 variants were selected for follow-up genotyping in the GWAS cohort using a Sequenom genotyping assay. Three SNPs (ECA10, 14, and 21) were highly associated with OC status.

A validation population of 162 Norwegian Standardbreds is now being genotyped for the same 240 variants as the discovery population. Putative risk alleles shown to be associated with disease status in both the discovery and validation populations can be considered true risk alleles for OC. Future analysis in other populations will determine if these genetic risk factors are universal or if they are breed- or lesion location-specific.