Heritability of metabolic traits associated with equine metabolic syndrome in Welsh ponies and Morgan horses

Norton, Elaine; Schultz, Nichol; McFarlane, Dianne; Geor, Raymond J.; Mickelson, James R.; McCue, Molly E.

doi:10.1111/evj.13053

Cited by 30 publications

(28 citation statements)

References 41 publications

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“…Within this cohort, we previously showed that baseline insulin had an h 2 SNP of 0.81 (SD = 0.11), with a mean h 2 SNP of 0.82 (mean SE: 0.12) after random subsetting . In this analysis, the h 2 SNP explained by genomic partitioning was 0.19 (SD = 0.086) or 24% of the total h 2 SNP for baseline insulin.…”

Section: Resultsmentioning

confidence: 57%

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

Norton

Avila

Schultz

et al. 2019

Veterinary Internal Medicne

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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.

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Section: Resultsmentioning

confidence: 57%

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

Norton

Avila

Schultz

et al. 2019

Veterinary Internal Medicne

Self Cite

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“…A similar variability between breeds has been demonstrated for insulin sensitivity and related biochemical parameters [194][195][196][197]. A recent study used genome-wide SNP data to estimate heritability of several traits known to be perturbed by EMS (glucose, insulin, measures of insulin sensitivity and dyslipidaemia) and found they were moderately to highly heritable [198]. Again, such within-breed comparisons are valuable but are likely to underestimate the true heritability in the equine population.…”

Section: Genetics Influence Equine Obesity Ems and Laminitismentioning

confidence: 66%

The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals

Wallis

Raffan

2020

Preprint

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Obesity is one of the most prevalent health conditions in humans and companion animals across the world. Obesity is associated with multiple health conditions across species including premature mortality. It is therefore of importance across the fields of medicine and veterinary medicine. The regulation of body weight is a homeostatic process vulnerable to disruption by genetic and environmental factors. It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarising the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats and horses, we review the similarities in obesity pathophysiology to humans and review those genetic studies that have been done to investigate them. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.

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“…SNP-based heritability estimates for traits associated with EMS (e.g., circulating insulin, glucose, ACTH, leptin) have bene reported to be quite high (Norton et al 2018). Genetic factors contributing to risk are also supported by varied rates of prevalence among, and variation in insulin responsiveness by breed (Treiber et al 2006; Bailey et al 2008; Bamford et al 2014).…”

Section: Genetics Of Complex Traitsmentioning

confidence: 99%

Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era

et al. 2019

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Summary The horse reference genome from the Thoroughbred mare Twilight has been available for a decade and, together with advances in genomics technologies, has led to unparalleled developments in equine genomics. At the core of this progress is the continuing improvement of the quality, contiguity and completeness of the reference genome, and its functional annotation. Recent achievements include the release of the next version of the reference genome (EquCab3.0) and generation of a reference sequence for the Y chromosome. Horse satellite-free centromeres provide unique models for mammalian centromere research. Despite extremely low genetic diversity of the Y chromosome, it has been possible to trace patrilines of breeds and pedigrees and show that Y variation was lost in the past ~2300 years due to selective breeding. The high-quality reference genome has led to the development of three different SNP arrays and whole genome sequences (WGS) of almost 2000 modern individual horses. The collection of WGS of hundreds of ancient horses is unique and not available for any other domestic species. These tools and resources have led to global population studies dissecting the natural history of the species and genetic makeup and ancestry of modern breeds. Most importantly, the available tools and resources, together with the discovery of functional elements, are dissecting molecular causes of a growing number of Mendelian and complex traits. The improved understanding of molecular underpinnings of various traits, continues to benefit the health and performance of the horse while also serving as a model for complex disease across species.

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Heritability of metabolic traits associated with equine metabolic syndrome in Welsh ponies and Morgan horses

Cited by 30 publications

References 41 publications

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

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

The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals

Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era

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