Identification of Genetic Loci Underlying Equine Metabolic Syndrome and Laminitis Risk in Welsh Ponies and Morgan Horses

Equine metabolic syndrome (EMS), a clustering of clinical signs including insulin resistance and dyslipidemia, is the most common cause of laminitis, a painful and life-threatening disease of the horse’s hoof. In a large across-breeds study of metabolic variation in horses, our lab demonstrated that EMS phenotypic variability is influenced by genetic and environmental factors.  Further, we demonstrated that certain features of the EMS phenotype are different between breeds. The objective of this project was to identify genomic regions contributing to EMS in two high risk breeds by performing a genome-wide association study (GWAS) in a cohort of 286 Morgans and 232 Welsh ponies (WP).  Individuals were genotyped on one of three SNP arrays (54,000 to 1,800,000 SNPs); the software program Beagle was used to generate a uniform set of makers across all three platforms. Quality control was performed using PLINK software. A relationship-matrix constructed from identity-by-descent estimation, and potential confounders such as gender and age, were included in a mixed logistic regression model using the R statistical software package, FastLMM. Within breeds genome wide significant loci were identified for several EMS traits.  Examples for Morgans include loci on chromosome 4 (ECA4), ECA19, and ECA 9 associated with insulin response, adiponectin and leptin levels, respectively, and examples for the WP include loci on ECA28, ECA19, and ECA24 associated with insulin response, adiponectin and baseline insulin levels.  Across breed analysis identified several significant associations which were not identified within breeds, for example associations on ECA13 and ECA19 for baseline ACTH levels.