The goal of this project is to advance understanding of factors that contribute to durability and longevity of career of racehorses, with particular emphasis on genetics. In doing so, we may also shed light on factors that could pre-dispose to catastrophic injuries suffered in racing or training. Such life-threatening injuries are genuine tragedies for the horses and their riders or drivers, trainers, and owners. Previous investigations have implicated many factors that may contribute to catastrophic injuries, including fitness, training regimes, track surfaces, prior health status of the horses involved, use of illegal drugs, and genetics. With so many variables and relatively few affected horses, it has been difficult to dissect genetic from environmental factors. Here we would focus on racehorses at the opposite end of the spectrum: those that have demonstrated durability and longevity in their careers. We propose that horses with extended successful racing careers have a sound genetic foundation that is coupled with excellent care and training. Recent publications from other investigators support this premise. In this project we would use genome-scale and epidemiological methods to identify genetic signatures correlated with longevity of racing career / durability. In Aim 1, using a Genome Wide Association Study (GWAS) and the 670k Equine Single Nucleotide Polymorphism (SNP) array, we would compare three groups of horses: 1) 100 aged Standardbreds with long racing careers and competitive race records; 2) 100 aged Standardbreds with long racing careers but relatively weak earnings records; 3) 100 or more control Standardbreds selected from previous studies. Specifically, we would test the hypothesis that the durable horses will show a GWAS peak on chromosome 7 that has been associated with racing starts in Thoroughbred horses. We may also be able to identify genetic regions that distinguish competitive from non-competitive horses with long racing careers. In Aim 2 we would obtain 20 x coverage whole genome sequence from 10 selected durable and 10 control Standardbreds for fine-scale comparison of regions identified in Aim 1. We have assembled an interdisciplinary team of investigators that includes members of the Horse Genome community of geneticists who have worked together over a multi-year period, and other veterinary scientists and clinicians with complementary expertise. This study will dovetail with a related project on durability in Thoroughbred horses that is currently under consideration for funding by the Hong Kong Jockey Club Research Foundation.