Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse

Introduction: Spontaneous rupture of tendons and ligaments is common in several species including humans. In horses, degenerative suspensory ligament desmitis (DSLD) an important acquired idiopathic disease a major energy-storing tendon-like structure. DSLD risk increased breeds, the Peruvian Horse. Affected horses have often been used for breeding before apparent. Breed predisposition suggests substantial genetic contribution, but heritability architecture not determined. Methods: To identify genomic regions associated with DSLD, we recruited reference population 183 Horses, phenotyped as cases or controls, undertook genome-wide association study (GWAS), regional window variance analysis using local partitioning, signatures selection (SOS) analysis, polygenic score (PRS) prediction risk. We also estimated trait from pedigrees. Results: Heritability was 1,927 at 0.22 ± 0.08. After establishing permutation-based threshold significance, 151 single nucleotide polymorphisms (SNPs) were identified by GWAS. Multiple enriched across genome, strong enrichment signals on chromosomes 1, 2, 6, 10, 13, 16, 18, 22, X chromosome. With SOS there 66 genes signature that present control group included TGFB3 gene. Pathways proteoglycan metabolism, extracellular matrix homeostasis, signal transduction pathways hedgehog signaling pathway. The best PRS predictive performance obtained when fitted 1% top SNPs Bayesian Ridge Regression model which achieved highest mean R 2 both probit logit liability scales, indicating performance. Discussion: conclude within-breed GWAS Horse has further confirmed moderate underlies multiple SNP associations novel tendinopathy candidate influencing variants include ones influence glycosaminoglycan pathways.