Royal Veterinary College Identifies Genetic Link to Fractures: Horses at Higher Genetic Risk Found to Have Reduced Collagen Type III Levels

A recent study conducted by the Royal Veterinary College has shed light on the genetic risks associated with fractures in Thoroughbred horses, unveiling a significant finding.

The research indicates that horses with lower levels of collagen type III have an elevated susceptibility to fractures.

This breakthrough discovery has empowered the Royal Veterinary College to develop advanced systems for identifying horses at high genetic risk, thereby enhancing the understanding, diagnosis, and management of fractures in Thoroughbreds. Ultimately, this research contributes to the overall improvement of the health and welfare of these magnificent animals.

Fractures pose a common challenge in Thoroughbred racehorses due to the immense forces their bones endure. Regrettably, fractures often lead to euthanasia, with approximately 60 horses per year requiring such measures on racecourses across the United Kingdom. Recognising the complexity of fractures, this condition is influenced by both environmental and genetic factors that impact a horse's vulnerability.

The study, spearheaded by Dr Debbie Guest, a senior research fellow at the Royal Veterinary College, employed a polygenic risk score to assess the disease risk associated with various genes. By analysing the distribution of these scores within the broader UK Thoroughbred population, the research team identified cells from horses at the extreme ends of the risk spectrum—those with very low or very high risks. Laboratory studies utilising these cells established a cell model that facilitated an in-depth investigation into the genetic factors contributing to fracture risk.

The research findings revealed that horses at a high genetic risk of fractures exhibit lower expression levels of collagen type III—a gene crucial for normal bone formation—in their bone cells. This disparity stems from a DNA sequence alteration in the regulatory region responsible for collagen III production.

To further validate the risk-scoring system, ongoing research is being conducted using another cohort of horses. Continued utilisation of this system and the cell model will unlock insights into additional genes and processes, deepening our understanding of why certain horses are inherently more susceptible to fractures than others.

Dr Debbie Guest underlined the significance of this study, stating, "Bone fractures are a major welfare concern in Thoroughbred racing. Despite extensive efforts to mitigate environmental risk factors, fractures unfortunately persist, revealing that some horses possess a genetic predisposition to this condition."

The development of a polygenic risk score for fractures enables the identification of horses at a high genetic risk, facilitating targeted use of diagnostic imaging and close monitoring of their bone health. Moreover, this groundbreaking study underscores the power of cell models in discerning the distinctions between bone cells from high and low-risk horses, thus unravelling the reasons behind heightened susceptibility. This knowledge is pivotal in the development of future interventions aimed at reducing catastrophic fractures in high-risk horses.

Funding for this research was provided by the Horserace Betting Levy Board, the Anne Duchess of Westminster Charitable Trust, and The Alborada Trust.