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Veterinary journal (London, England : 1997)2025; 312; 106347; doi: 10.1016/j.tvjl.2025.106347

Exploring the genetic influences on equine analgesic efficacy through genome-wide association analysis of ranked pain responses.

Abstract: Multimodal analgesic administration is a promising strategy for mitigating side effects typically associated with analgesia; nevertheless, variation in analgesic effectiveness still poses a considerable safety concern for both horses and veterinarians. Pharmacogenomic studies have started delving into genetic influences on varying drug effectiveness and related side effects. However, current findings have narrow implications and are limited in their ability to individualize analgesic dosages in horses. Hydromorphone and detomidine were administered to a cohort of 48 horses at standardized time intervals, with dosage rates recorded. Analgesic effectiveness was scored (1-3) based on pain response to dura penetration during cerebrospinal fluid centesis. Genome-wide association (GWA) analyses identified two SNVs passing the nominal significance threshold (P < 1 ×10) in association with analgesic effectiveness. One SNV identified on chromosome 27 (rs1142378599) is contained within the LOC100630731 disintegrin and metalloproteinase domain-containing protein 5 gene. The second identified SNV is an intergenic variant located on chromosome 29 (rs3430772468) These SNVs accounted for 26.11 % and 31.72 % of explained variation in analgesic effectiveness respectively, with all eight of the horses with the lowest analgesic effectiveness expressing the A/C genotype at rs3430772468, with six of which also expressing the C/T genotype at rs1142872965. Whilst highlighting the multifactorial nature of analgesic efficacy, this study serves as an important step in the application of genome-wide approaches to better understand genetic factors underpinning commonly observed variation in analgesic effectiveness in horses, with the goal of tailoring analgesic dosage to minimize commonly observed side effects and improve the outcomes of equine pain management.
Publication Date: 2025-04-10 PubMed ID: 40216012DOI: 10.1016/j.tvjl.2025.106347Google Scholar: Lookup
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Summary

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This research investigates how genetic factors in horses may affect the efficacy of pain medication. Using a genome-wide approach, the study found two specific genetic variations that may explain the observed differences in how horses react to analgesics.

Study Design and Methodology

  • The researchers orchestrated this study to explore the possibility of genetic influences on the variability of drug effectiveness in horses. Specifically, they directed their focus on analgesics – the class of medicines used for pain relief.
  • The study involved administering two types of analgesics, hydromorphone and detomidine, to a cohort of 48 horses at regular intervals. The administered doses were recorded for reference.
  • The research team rated the effectiveness of the analgesics using a scoring system (1-3) that gauged the horses’ pain reaction to dura penetration (a noticeable equine pain response) during cerebrospinal fluid centesis – a procedure of obtaining a sample of cerebrospinal fluid.

Findings of the Study

  • The researchers conducted Genome-wide association (GWA) analyses and unveiled two specific genetic variations, termed Single Nucleotide Variants (SNVs), which showed significant association with analgesic effectiveness in horses.
  • One of the identified SNVs (rs1142378599) is located on the 27th chromosome within the LOC100630731 gene, which encodes for disintegrin and metalloproteinase domain-containing protein 5. The other SNV (rs3430772468) is an intergenic variant occurring on chromosome 29.
  • These identified SNVs contribute to a significant part of the variation in analgesic effectiveness – accounting for 26.11 % and 31.72 % of the explained variation, respectively.
  • Interestingly, all eight horses that demonstrated the lowest analgesic effectiveness harbored the A/C genotype at rs3430772468, while six of them also carried the C/T genotype at rs1142872965.

Implications of the Study

  • This study underscores the complex nature of analgesic efficacy and its multifactorial determinants.
  • Further, the association of specific SNVs with analgesic efficacy can enhance our understanding of genetic influences on drug effectiveness – potentially paving the way for more personalized pain management in horses.
  • These findings can aid in individualizing analgesic doses, thus minimizing common adverse side-effects and improving outcomes of equine pain management.

Cite This Article

APA
Bacon EK, Donnelly CG, Finno CJ, Haase B, Velie BD. (2025). Exploring the genetic influences on equine analgesic efficacy through genome-wide association analysis of ranked pain responses. Vet J, 312, 106347. https://doi.org/10.1016/j.tvjl.2025.106347

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 312
Pages: 106347
PII: S1090-0233(25)00051-6

Researcher Affiliations

Bacon, Elouise K
  • Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, NSW, Australia. Electronic address: elouise.bacon@sydney.edu.au.
Donnelly, Callum G
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA; Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithica, NY, 14850, USA.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Haase, Bianca
  • School of Veterinary Science, University of Sydney, NSW, Australia.
Velie, Brandon D
  • Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, NSW, Australia.

Conflict of Interest Statement

Declaration of Competing Interest The authors have nothing to declare

Citations

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