Study Identifies Possible Fracture-Risk Genes

New research from the Royal Veterinary College (RVC) has identified more than 100 genes that may contribute to bone fracture risk in Thoroughbreds. These findings will inform further research into genetic risk factors, contributing to health and well-being efforts and supporting the development of novel interventions to reduce fracture risk in horses. Bone fractures are common in Thoroughbred racehorses, due to the forces the bones can experience. Bone fractures are sadly a leading cause of euthanasia, with approximately 60 horses having to be euthanised on UK racecourses each year. However, fractures are a complex condition, with both environmental and genetic risk factors affecting a horse's susceptibility. Led by Dr Debbie Guest, Senior Research Fellow at the RVC, a team of researchers used a polygenic risk score for fracture risk to establish a new model with stem cells to make bone-forming cells from horses at both high and low risk. The team measured every gene that was expressed by the cells to identify those with different expression levels in the bone cells from horses at higher versus those at lower risk. The study identified 112 genes that may be involved in fracture risk and demonstrated that many of these genes regulate the bone matrix. However, a large number of the genes have never been studied in bone before and more research is needed to understand the function of these genes in bone cells and how they contribute to fracture risk. This is the second study in a series of research, exploring genetic mechanisms behind fracture risk. A previous study found that collagen type III, a gene which is required for normal bone formation, is expressed at lower levels in bone cells from horses with a high genetic risk of fracture. This is because they have a change in their DNA sequence in the region which controls how much collagen III is produced. Additional research is now being conducted to validate the risk-scoring system in another cohort of horses. Further studies using this system and cell model will help to identify other genes and processes to better understand why some horses are inherently more susceptible to fracture than others. This will help veterinary practitioners to better support and treat thoroughbreds. Dr Debbie Guest, Senior Research Fellow at the RVC, said: "Bone fractures are a common problem in Thoroughbred racehorses, despite many changes to racecourses over the years to reduce environmental risk factors. We know that fracture risk has a genetic component and we have previously developed a polygenic risk score for fracture to allow us to identify horses at increased risk. "In this study, we have identified many new genes which have altered expression in bone cells from high-risk horses. For some of these genes, we know that they play a role in regulating the bone matrix. We can now begin to develop a deeper understanding of how bone tissue is altered in high-risk horses and new interventions to reduce their risk". The research was funded by the Horserace Betting Levy Board, the Anne Duchess of Westminster Charitable Trust and The Alborada Trust.