Genome-Wide Association Analysis Of Shivers In Belgian Horses

Rhythmic locomotor patterns are regulated by networks of spinal interneurons called central pattern generators (CGP). Horses provide unique models to study the molecular mechanisms that govern CPGs because centuries of selective breeding has fixed specific gaits within breeds and selection pressure has also resulted in novel inherited equine disorders of locomotion.  In particular, Shivers is an equine disorder that occurs in Draft, Warmblood and Thoroughbred breeds which distinctively affects backwards walking while forward gaits are normal. Horses, particularly tall geldings, present with abduction, hyperflexion and muscle tremors in the pelvic limbs during backwards walking and manually picking up a hindlimb.  A whole genome association analysis (GWAS) was performed across 54,000 single nucleotide polymorphisms (SNPs) on 51 affected (27 male, 24 female) and 98 control (40 male, 58 female) North American Belgian Draft horses using the Illumina Equine54KSNP platform. Genomic inflation was minimal (λGC=1.08).  Logistic regression was performed with sex as a covariate and an association signal was found between Shivers phenotype and a region on ECA8 spanning 166 kB that included four SNPs (highest p_unadjusted 2.53 x 10^-5; p_genome 0.10 following 10,000 permutations). Additional cases and controls or higher density SNP chips are necessary to achieve genome wide significance.  To further evaluate this region, whole genome sequencing is underway in two male Shivers-affected Belgian horses and two male age-matched controls.