External supporting research Metabolic health & insulin dysregulation Peer reviewed EXT-S09

Genetics & Equine Metabolic Syndrome

A genome-wide study of Welsh ponies and Morgan horses found numerous genetic regions associated with equine metabolic syndrome traits, supporting EMS as a complex polygenic condition involving both shared and breed-specific genetic risk.

Original study title

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

Equine metabolic syndrome Insulin dysregulation Genetics Genetic risk Glucose metabolism Lipid metabolism Inflammation Laminitis risk

Study at a glance

Year 2019

Study type Genome-wide association study and meta-analysis

Sample 550 horses and ponies: 264 Welsh ponies and 286 Morgan horses

Population Welsh ponies and Morgan horses from two breeds considered at increased risk of equine metabolic syndrome

Publication Peer-reviewed journal article

EquiNectar tested? No

Peer reviewed Yes

Open access Yes

Relationship External supporting research

286

Morgan horses included in genome-wide analyses

264

Welsh ponies included in genome-wide analyses

EMS-related traits analyzed

Genomic regions shared across breeds in meta-analysis

Research question

What did the researchers want to understand?

Which genomic regions are associated with equine metabolic syndrome-related traits in Welsh ponies and Morgan horses, and which genetic risk regions are shared between or specific to these two breeds?

Researchers

Study authors

Molly McCue

University of Minnesota

James Mickelson

University of Minnesota

Dianne McFarlane

Oklahoma State University

Elaine Norton

University of Minnesota

Nichol Schultz

University of Minnesota

Ray Geor

Massey University

Research organizations

Research institutions

University of Minnesota

University
United States

Massey University

University
New Zealand

Oklahoma State University

University
United States

Methodology

How the study was conducted

Study design

This was a genome-wide association study examining genetic susceptibility to equine metabolic syndrome in Welsh ponies and Morgan horses.

Genome-wide association analyses were conducted separately within the two breeds using 12 metabolic phenotypes associated with EMS.

The Welsh pony analyses included 264 animals and the Morgan horse analyses included 286 animals.

The researchers identified genomic regions statistically associated with individual metabolic traits and then used meta-analysis to identify regions shared across breeds.

Associated regions were prioritized according to evidence across breeds and metabolic phenotypes.

Genes located within prioritized regions were examined to identify biological pathways potentially involved in EMS.

The approach allowed researchers to investigate both shared genetic susceptibility and breed-specific genetic architecture.

What was measured

Researchers performed within-breed genome-wide association analyses for 12 phenotypic traits associated with equine metabolic syndrome in Welsh ponies and Morgan horses.

The phenotypes represented several components of EMS, including measures related to insulin regulation, glucose metabolism, adiposity and lipid metabolism.

Genome-wide genetic data were tested for associations with these metabolic phenotypes within each breed.

The researchers then conducted meta-analysis to identify genomic regions shared between breeds.

Associated regions were prioritized according to whether they were shared between breeds, shared across multiple metabolic traits or identified within individual genome-wide analyses.

Candidate genes within prioritized genomic regions were subsequently examined for enrichment of biological pathways potentially relevant to equine metabolic syndrome.

Study findings

Key results

• Genome-wide association analyses were conducted for 12 equine metabolic syndrome-related traits.

• The analyses included 264 Welsh ponies and 286 Morgan horses.

• Researchers identified 303 associated genomic regions in Welsh ponies and 142 in Morgan horses.

• Meta-analysis identified 65 genomic regions shared between the two breeds.

• Prioritization identified 56 high-priority regions in Welsh ponies and 39 high-priority regions in Morgan horses.

• Prioritized Welsh pony regions contained 1,853 candidate genes.

• Prioritized Morgan horse regions contained 1,167 candidate genes.

• Candidate genes were enriched in biological pathways associated with glucose metabolism, lipid metabolism and inflammation.

• Both shared and breed-specific genetic associations were identified.

• The authors concluded that equine metabolic syndrome is a complex polygenic trait involving numerous genetic risk alleles.

• A single genetic variant is therefore unlikely to provide an accurate predictive test for EMS.

Interpretation

What do the findings mean?

The findings provide strong evidence that equine metabolic syndrome has a complex polygenic genetic architecture.

Genome-wide analyses identified numerous genomic regions associated with 12 metabolic traits in Welsh ponies and Morgan horses.

Meta-analysis identified 65 genomic regions shared between breeds, while other associations appeared to be breed specific.

Prioritized genomic regions contained candidate genes associated with biological pathways involving glucose metabolism, lipid metabolism and inflammation.

The findings therefore support a model in which inherited susceptibility to EMS reflects the combined influence of multiple genetic variants rather than one dominant genetic cause.

Genetic susceptibility should also not be interpreted as genetic destiny. Equine metabolic syndrome develops within a wider interaction between inherited biology, nutrition, body condition, exercise and other environmental factors.

The research improves understanding of why individual horses and different breeds may vary in metabolic susceptibility, but further research is required before these findings can be used for reliable individual genetic risk prediction.

In practice

Why this research matters

Equine metabolic syndrome should not be viewed as a condition caused by a single gene or a single management factor.

This study found evidence for numerous genetic regions associated with metabolic traits in two breeds considered at increased risk of EMS.

Some genetic regions were shared between Welsh ponies and Morgan horses, while others differed between breeds. This suggests that inherited susceptibility to EMS is complex and may vary between populations.

The findings also indicate that a simple genetic test based on one variant is unlikely to accurately predict an individual horse's overall EMS risk.

For owners and professionals, genetic susceptibility does not mean that metabolic disease is inevitable. Identifying horses at greater risk may instead make appropriate bodyweight management, diet, exercise, monitoring of insulin regulation and veterinary assessment particularly important.

The study supports an individualized approach to metabolic health rather than assuming that all horses respond to the same environment or feeding program in the same way.

Research transparency

Study limitations

The study focused on Welsh ponies and Morgan horses, two populations selected because of their relatively high risk of equine metabolic syndrome. The genetic associations identified may therefore not transfer directly to other horse breeds.

Genome-wide association studies identify statistical relationships between genomic regions and phenotypes. They do not by themselves demonstrate that a particular genetic variant causes equine metabolic syndrome.

The researchers identified hundreds of associated genomic regions containing thousands of candidate genes. Further work is required to narrow these regions and identify specific functional variants.

The study analyzed multiple related EMS phenotypes rather than treating the syndrome as a single simple trait. This reflects the biological complexity of EMS but also increases the complexity of interpreting individual genetic associations.

Some associated regions were breed specific, emphasizing that genetic risk identified in one breed should not automatically be assumed to apply to another.

The results cannot currently be translated into a simple diagnostic genetic test. The authors concluded that a single genetic variant would not provide sufficient information to accurately predict EMS risk.

EquiNectar context

How this research relates to EquiNectar

This research did not test EquiNectar and was conducted independently of Tharos Ltd.

Its relevance to the EquiNectar Science Center is primarily through the wider context of metabolic health, insulin regulation and individualized horse management.

The study demonstrates that equine metabolic syndrome is a complex polygenic condition. Numerous genetic regions were associated with EMS-related traits, with some genetic risk shared between Welsh ponies and Morgan horses and other associations appearing to be breed specific.

Genes within prioritized regions were enriched for biological pathways associated with glucose metabolism, lipid metabolism and inflammation, all of which are relevant to the biology of EMS.

This research reinforces an important distinction between genetic susceptibility and modifiable management factors. Genetics may influence an individual horse's underlying risk, while diet, body condition, exercise and veterinary management remain important factors that can be addressed in practice.

The study provides no evidence that EquiNectar prevents, treats or modifies genetic risk for equine metabolic syndrome.

Tharos / EquiNectar involvement

None. This research was conducted independently of Tharos Ltd and EquiNectar. EquiNectar was not evaluated in the study.

EquiNectar evaluated No

Transparency

Funding & competing interests

Funding statement

The research was funded by Foundation for the National Institute of Health grant T32OD010996; Morris Animal Foundation grant D14EQ-033 and doctoral fellowship D17EQ-402; and the National Institute of Food and Agriculture grant 2009-55205-052542012-67015-19432.

Competing interests

The authors declared no conflict of interest.

Source record

Publication details

Journal

Genes

Publisher

MDPI

Year

2019

Volume

Issue

Pages / article

893

DOI

10.3390/genes10110893

PMID

31698676

Species

Horse

Population

Welsh ponies and Morgan horses from two breeds considered at increased risk of equine metabolic syndrome

Sample

550 horses and ponies: 264 Welsh ponies and 286 Morgan horses

Setting

Multi-institutional genetic study of Welsh ponies and Morgan horses

License

CC BY 4.0

View original source ↗ Read full text ↗

Recommended citation

Norton E, Schultz N, Geor R, McFarlane D, Mickelson J, McCue M. Genome-Wide Association Analyses of Equine Metabolic Syndrome Phenotypes in Welsh Ponies and Morgan Horses. Genes. 2019;10(11):893. doi:10.3390/genes10110893.

Genetics & Equine Metabolic Syndrome

What did the researchers want to understand?

Study authors

Molly McCue

James Mickelson

Dianne McFarlane

Elaine Norton

Nichol Schultz

Ray Geor

Research institutions

University of Minnesota

Massey University

Oklahoma State University

How the study was conducted

Key results

What do the findings mean?

Why this research matters

Study limitations

How this research relates to EquiNectar

Funding & competing interests

Funding statement

Competing interests

Publication details

Related practical resources

Genetics & Equine Metabolic Syndrome