Identification of a Genetic Locus Associated with Height and Fasting Insulin in Welsh Ponies and Morgan Horses

Ponies have higher fasting insulin concentrations and are more insulin resistant than horses. In humans and mice, genetic alleles resulting in small skeletal size have also been associated with alterations in insulin and glucose metabolism. We hypothesized genetic that loci affecting height in ponies have pleiotrophic effects on metabolic traits. Pearson’s correlation coefficient identified an inverse relationship between wither height and fasting insulin in 298 Welsh ponies (WP) (-0.26; 95% CI -0.36 to -0.15; p-value: <6.4e-06). Using genome-wide association studies were performed for height and fasting insulin in 232 WP and 286 Morgan horses, a locus on chromosome 6 was significantly associated with height and fasting insulin in the WP, but not in Morgans. HMGA2 was identified as a potential candidate gene, due to a recently identified C.83G>A variant associated with height in Shetland ponies. To date, we have genotyped 250 WP and 60 Morgans for this variant and identified an allelic frequency of 0.802 and 0.375, respectively for the A allele. Correlations were identified for the additive effect of the A allele on height [0.59; 95% CI -0.66 to -0.51; p-value: <2.2e-16 (WP) and 0.69; 95% CI -0.81 to -0.59; p-value: 7.4e-10 (Morgan)] and baseline insulin values [0.22; 95% CI 0.10 to 0.34; p-value 3.5e-04.22 (WP) and 0.46; 95% CI 0.23 to 0.64; p-value: 2.1e-04 (Morgan)]. These data suggest that the variant in HMGA2 may have an effect on both height and insulin, which has important implications for equine metabolic syndrome susceptibility.