Background: Ponies are highly susceptible to metabolic derangements including hyperinsulinemia, insulin resistance, and adiposity. Hypothesis/Objectives: Genetic loci affecting height in ponies have pleiotropic effects on metabolic pathways and increase the susceptibility to equine metabolic syndrome (EMS). Animals: Two hundred ninety-four Welsh ponies and 529 horses. Methods: Retrospective study of horses phenotyped for metabolic traits. Correlations between height and metabolic traits were assessed by Pearson's correlation coefficients. Complementary genome-wide analysis methods were used to identify a region of interest (ROI) for height and metabolic traits, determine the fraction of heritability contributed by the ROI, and identify candidate genes. Results: There was an inverse relationship between height and baseline insulin (−0.26) in ponies. Genomic signature of selection and association analyses for both height and insulin identified the same ~1.3 megabase region on chromosome 6 that contained a shared ancestral haplotype between these traits. The ROI contributed ~40% of the heritability for height and ~20% of the heritability for insulin. High-mobility group AT-hook 2 was identified as a candidate gene, and Sanger sequencing detected a c.83G>A (p.G28E) variant associated with height in Shetland ponies. In our cohort of ponies, the A allele had a frequency of 0.76, was strongly correlated with height (−0.75), and was low to moderately correlated with metabolic traits including: insulin (0.32), insulin after an oral sugar test (0.25), non-esterified fatty acids (0.19), and triglyceride (0.22) concentrations. Conclusions and Clinical Importance: These data have important implications for identifying individuals at risk for EMS.
Bibliographical noteFunding Information:
Foundation for the National Institutes of Health, Grant/Award Number: T32 OD010993; Morris Animal Foundation, Grant/ Award Number: D14EQ-033; National Institute of Food and Agriculture, Grant/Award Number: 2009-55205-052542012-67015 -19432
This work was presented at the 2016 American College of Veterinary Internal Medicine Forum, Denver, CO; Havemeyer Endocrinology Summit, January 2017, Miami, FL; and Equine Science Society Annual Meeting, May 2017, Minneapolis, MN.
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
- equine metabolic syndrome
- insulin dysregulation