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Home / Equine Research Bank / Equine Vet J / A genome-wide association study for recurrent laryngeal neur...
Equine veterinary journal2025; doi: 10.1111/evj.14461

A genome-wide association study for recurrent laryngeal neuropathy in the Thoroughbred horse identifies a candidate gene that regulates myelin structure.

Abstract: Equine recurrent laryngeal neuropathy (RLN) is an economically important upper respiratory tract (URT) disease with a genetic contribution to risk, but genetic variants independent of height have not been identified for Thoroughbreds. The method of clinical assessment for RLN is critical to accurately phenotype groups for genetic studies. Objective: To identify genetic risk loci for RLN in Thoroughbreds in a genome-wide association study (GWAS) following high-resolution phenotyping. Methods: Case-control. Methods: Thoroughbred horses were characterised as RLN cases and controls using resting and exercising URT endoscopic examinations and laryngeal ultrasonography, with the case-cohort supplemented using a questionnaire. Genotypes for 43 831 autosomal single-nucleotide polymorphisms (SNPs) from n = 235 horses (n = 110 cases; n = 125 controls) were used to estimate trait heritability and identify significantly associated SNPs in a GWAS. Haplotypes were examined in cases and controls and risk allele frequencies were examined in a population cohort (n = 3126). Results: Heritability was h = 0.30 including sex and 5PCs as covariates. A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was significantly associated with RLN. Six index SNPs with allelic effect sizes OR = 1.5-2.9 were identified on ECA1, ECA14, and ECA20 close to candidate genes ATPA10, KCNN2, and TFAP2A. Eleven ECA20 SNPs defined seven haplotypes with homozygous H2/H2 horses having a 3.1× higher risk of RLN. Risk alleles segregate in the population, and stallions are carriers. Conclusions: The main study population was young. Horses in the control group had no evidence of RLN as 2- or 3-year olds but may have developed RLN later. Conclusions: Genetic markers for RLN were identified which may be useful for the development of a polygenic risk score. Candidate genes with functions in neuropathies may further the understanding of RLN pathobiology. Unassigned: La neuropatía laríngea recurrente (RNL) en el equino es una enfermedad del tracto respiratorio superior (URT) económicamente importante con una contribución genética al riesgo, cuyas variantes genéticas independientes a la altura no han sido identificadas en el Fina Sangre de Carrera. El método de diagnóstico clínico de RNL es crítico para determinar grupos fenotípicos para estudios genéticos. Objective: Identificar loci de riesgo genético para RLN en Fina Sangre de Carrera en un estudio de asociación de genoma generalizado (GWAS) después de fenotipificación de alta resolución. DISEÑO DEL ESTUDIO: Caso‐control. MÉTODOS: Caballos Fina Sangre de Carrera fueron caracterizados como casos RNL y controles usando examinaciones en reposo y durante ejercicio por endoscopia del URT y ultrasonido de la laringe, con la cohorte de casos suplementados usando un cuestionario. Lo genotipos de 43 831 polimorfismos autosomales de nucleótido singular (SNPs) de n = 235 caballos (n = 110 casos; n = 125 controles) fueron usados para estimar la heredabilidad del rasgo e identificar SNPs asociados en forma significativa en un GWAS. Haplotipos fueron examinados en los casos y controles, y las frecuencias de los alelos de riesgo fueron examinadas en una cohorte de la población (n = 3126). Results: La heredabilidad fue de h = 0.30 incluyendo sexo y 5PCs como covariantes. Un SNP en ECA20 localizado entre los genes candidatos DAAM2 y LRFN2, fue asociado en forma significativa con la RLN. Seis SNPs índices con efecto alélico de tamaño OR = 1.5–2.9 fueron identificados en ECA1, ECA14 y ECA20 cerca de los genes candidatos ATPA10, KCNN2, y TFAP2A. Once SNPs en ECA20 definieron siete haplotipos en caballos homocigotos H2/H2 de tener un riesgo 3.1× mayor de RLN. Los alelos de riesgo son segregados en la población y los potros son portadores. Unassigned: La población principal era joven. Los caballos en el grupo control no tenía evidencia de RLN a los dos o tres años, pero pueden haber desarrollado RLN más tarde. Conclusions: Se identificaron marcadores genéticos para RLN los cuales pueden ser útiles para desarrollar un puntaje de riesgo poligénico. Los genes candidatos con funciones en neuropatías podrían aumentar el conocimiento de la patobiología de RLN.
© 2025 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2025-01-10 PubMed ID: 39791379DOI: 10.1111/evj.14461Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research conducted a genetic study on Thoroughbred horses to identify genes associated with recurrent laryngeal neuropathy (RLN), a significant respiratory disease. The study found SNPs (single-nucleotide polymorphisms), particularly on gene ECA20, associated with higher risks of RLN. Further exploration on the mentioned SNPs could offer insights into understanding the disease and developing genetic risk scores.

Objective of the Study

  • The main aim of this study was to identify the genetic risk factors of RLN in Thoroughbred horses by conducting a GWAS (genome-wide association study). This research aimed to offer an accurate genetic framework and thus contribute to the broader understanding and possible future treatment of the disease.

Methods Used in The Study

  • Researchers characterized Thoroughbred horses as RLN cases and controls by using resting and exercising upper respiratory tract (URT) endoscopic examinations and laryngeal ultrasonography.
  • The case-cohort was supplemented by a questionnaire to gather additional data.
  • The genotypes for 43,831 autosomal single-nucleotide polymorphisms (SNPs) from 235 horses were used to estimate trait heritability and identify significantly associated SNPs in the GWAS.
  • Haplotypes were examined in cases and controls, and risk allele frequencies were examined in a population cohort.

Findings from The Study

  • The heritability factor was found to be 0.30 when accounting for sex and 5PCs (Principal Components) as covariates. This highlights a certain level of genetic predisposition to the disease.
  • A SNP on gene ECA20 located between the DAAM2 and LRFN2 genes was found to be significantly associated with RLN. Six index SNPs were identified on genes ECA1, ECA14, and ECA20 close to candidate genes ATPA10, KCNN2, and TFAP2A.
  • Seven haplotypes were defined by eleven ECA20 SNPs, with homozygous H2/H2 horses having a 3.1x higher risk of RLN. This means there was a frequent presence of certain SNPs in horses with RLN, suggesting a linkage to the disease.

Conclusions from The Study

  • The study found genetic markers for RLN which can be useful in the development of a polygenic risk score. This could be applied in predictive tests for young Thoroughbred horses.
  • It was observed that the control group had no evidence of RLN as 2- to 3-year olds, but they may have developed RLN at a later age. This indicates the possibility of late-onset of the disease.
  • The candidate genes identified, which are known to have roles in neuropathies, could provide further insight into the pathobiology of RLN, advancing our understanding of neuropathic diseases in general.

Cite This Article

APA
McGivney CL, McGivney BA, Farries G, Gough KF, Han H, Holtby AR, MacHugh DE, Katz LM, Hill EW. (2025). A genome-wide association study for recurrent laryngeal neuropathy in the Thoroughbred horse identifies a candidate gene that regulates myelin structure. Equine Vet J. https://doi.org/10.1111/evj.14461

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

McGivney, Charlotte L
  • UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
McGivney, Beatrice A
  • Plusvital Ltd., The Highline, Dun Laoghaire Industrial Estate, Dublin, Ireland.
Farries, Gabriella
  • UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Gough, Katie F
  • UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Han, Haige
  • Plusvital Ltd., The Highline, Dun Laoghaire Industrial Estate, Dublin, Ireland.
Holtby, Amy R
  • Plusvital Ltd., The Highline, Dun Laoghaire Industrial Estate, Dublin, Ireland.
MacHugh, David E
  • UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
  • UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Katz, Lisa Michelle
  • UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
Hill, Emmeline W
  • UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
  • Plusvital Ltd., The Highline, Dun Laoghaire Industrial Estate, Dublin, Ireland.

Grant Funding

  • 11-PI-1166 / Science Foundation Ireland

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