Evaluation of an HMGA2 variant for pleiotropic effects on height and metabolic traits in ponies

Elaine M. Norton, Felipe Avila, Nichol E. Schultz, James R. Mickelson, Ray J. Geor, Molly E. McCue

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)942-952
Number of pages11
JournalJournal of veterinary internal medicine
Issue number2
StatePublished - Mar 1 2019

Bibliographical note

Funding 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

Funding Information:
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.

Publisher Copyright:
© 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
  • genetics
  • horses
  • insulin dysregulation


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