Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse
Authors: M. Momen, Kiley Brauer, Margaret M Patterson, Susannah J. Sample, Emily E. Binversie, B. Davis, E. G. Cothran, G. Rosa, S. Brounts, P. Muir, N. G. Hossein-Zadeh, J. Halper
Journal: Frontiers in Genetics
Summary
# Editorial Summary: Genetic Basis of DSLD in Peruvian Horses Degenerative suspensory ligament desmitis (DSLD) causes catastrophic ligament failure in horses, with Peruvian breeds showing marked predisposition, yet the underlying genetic mechanisms remain poorly characterised. Researchers conducted a genome-wide association study (GWAS) in 183 phenotyped Peruvian horses alongside pedigree analysis in a larger population of 1,927 animals, identifying 151 DSLD-risk SNPs and estimating trait heritability at 0.22—confirming a moderate but substantial genetic contribution. Multiple genomic regions showed enriched heritability signals across nine chromosomes, with 66 genes displaying selection signatures in affected horses; notably, these genes cluster in pathways governing glycosaminoglycan metabolism, extracellular matrix remodelling, and hedgehog signalling. The researchers developed a polygenic risk score (PRS) using Bayesian regression that achieved strong predictive performance, demonstrating practical utility for identifying at-risk individuals before clinical disease manifests. Given that affected horses are often bred unknowingly before symptoms appear, this PRS offers farriers, veterinarians, and breeders an evidence-based tool for genetic screening and selective breeding decisions—though validation across other breed populations will be essential before broad clinical implementation.
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Practical Takeaways
- •DSLD has a moderate genetic basis (22% heritability), meaning breeding decisions should consider genetic risk; polygenic risk scoring may enable identification of at-risk horses before clinical signs appear
- •Multiple genes across multiple chromosomes contribute to DSLD risk, suggesting no single genetic test will identify all susceptible horses—genomic screening protocols should focus on high-risk breeds like Peruvians
- •The involvement of extracellular matrix and proteoglycan metabolism pathways suggests potential therapeutic targets (e.g., managing inflammation and matrix remodeling) and highlights why early intervention in nutritional support and controlled exercise may be important for genetically predisposed horses
Key Findings
- •DSLD heritability estimated at 0.22 ± 0.08 in Peruvian horses, indicating moderate genetic contribution to disease risk
- •151 DSLD-associated SNPs identified through GWAS with enriched local heritability signals on 9 chromosomes
- •Polygenic risk score using top 1% of SNPs achieved strong predictive performance (R² on probit and logit liability scales)
- •Pathways enriched in DSLD cases include proteoglycan metabolism, extracellular matrix homeostasis, and hedgehog signaling pathway with TGFB3 gene showing selection signature