Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses

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

doi:10.3390/genes10110893

Cited by 11 publications

(13 citation statements)

References 62 publications

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“…Thus, it is not surprising that we were not powered to detect loci exceeding our genome-wide significant threshold with GEMMA. However, we have previously described an improved linear mixed model for the analysis of complex traits with small sample sizes [ 22 ]. This approach improved our power to detect the loci on chromosomes 6, 11, and 28, as well as identify additional loci on chromosomes 1 and 20.…”

Section: Discussionmentioning

confidence: 99%

“…A mixed model analysis in the software program Genome-Wide Efficient Mixed Model Analysis v 0.98.4 (GEMMA) [ 21 ] was used with the imputed genotype data and the inclusion of the fixed effects and a standard GRM. We also used an improved mixed linear model which we previously utilized to increase power in cohorts with a relatively small sample size [ 22 ]. Briefly, this algorithm implements a three steps process.…”

Section: Methodsmentioning

confidence: 99%

“…The boundaries of the regions associated with BCC identified on GWA were defined based on the breakdown of linkage disequilibrium (LD) as previously described [ 22 ]. Briefly, PLINK was used to measure pairwise LD for each SNP exceeding the suggestive or genome-wide significant threshold in the GWA [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

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Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies

Norton

Minor

Taylor³

et al. 2021

Genes

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An episodic nervous system disorder triggered by strenuous exercise, termed border collie collapse (BCC), exists in border collies and related breeds. The genetic basis of BCC is unknown but is believed to be a complex genetic disorder. Our goal was to estimate the heritability (h2SNP) of BCC, define its underlying genetic architecture, and identify associated genomic loci using dense whole-genome single-nucleotide polymorphism (SNP) genotyping data. Genotype data were obtained for ~440,000 SNPs from 343 border collies (168 BCC cases and 175 controls). h2SNP was calculated to be 49–61% depending on the estimated BCC prevalence. A total of 2407 SNPs across the genome accounted for nearly all the h2SNP of BCC, with an estimated 2003 SNPs of small effect, 349 SNPs of moderate effect, and 56 SNPs of large effect. Genome-wide association analyses identified significantly associated loci on chromosomes 1, 6, 11, 20, and 28, which accounted for ~5% of the total BCC h2SNP. We conclude that BCC is a moderately- to highly-heritable complex polygenetic disease resulting from contributions from hundreds to thousands of genetic variants with variable effect sizes. Understanding how much the BCC phenotype is determined by genetics and whether major gene mutations are likely to exist inform veterinarians and working/stock dog communities of the true nature of this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies

Norton

Minor

Taylor³

et al. 2021

Genes

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“…Norton et al [ 219 ] recently performed a GWAS focussed on EMS in a larger equine cohort ( n = 550) representing two high-risk breeds (Welsh ponies and Morgan horses). By collecting rich metabolic data, they were able to test for association with multiple “endophenotypes”, more precise biochemical markers of insulin-related traits.…”

Section: Obesity and Related Metabolic Disease In Horsesmentioning

confidence: 99%

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

Wallis

Raffan

2020

Genes

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Obesity is one of the most prevalent health conditions in humans and companion animals globally. It is associated with premature mortality, metabolic dysfunction, and multiple health conditions across species. Obesity is, therefore, of importance in the fields of medicine and veterinary medicine. The regulation of adiposity is a homeostatic process vulnerable to disruption by a multitude of 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 summarise 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 compare the similarities in obesity pathophysiology to humans and review the genetic studies that have been previously reported in those species. 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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“…Norton et al [203] recently performed a GWAS focussed on EMS in a larger equine cohort (n=550) representing two high-risk breeds (Welsh ponies and Morgan horses). By collecting rich metabolic data, they were able to test for association with multiple 'endophenotypes', more precise biochemical markers of insulin related traits.…”

Section: Gwas For Ems and Related Traitsmentioning

confidence: 99%

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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Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses

Cited by 11 publications

References 62 publications

Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies

Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies

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

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

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