Genome-Wide Association Study of Shivers in Clydesdale Horses

Shivers is a neuromuscular disease affecting the coordination of movement in Draft, Warmblood, and Thoroughbred horses. Affected individuals display prolonged hyperflexion or extension of the hind limbs and muscle tremors, particularly when backing-up.  Shivers is often observed within family groups, especially tall (>16.3 hand) geldings, suggesting that susceptibility is heritable with expression affected by both size and gender.  To identify genomic regions that may contribute to the disease, Clydesdale horses were genotyped on the Equine70 BeadChip.  Affected individuals (12 male, 3 female) had difficulty backing up with limb hyperextension and tremors of the tail head, and also showed variable circumduction at a walk.  Clinically normal, control horses (12 male, 17 female) were matched when possible to the cases’ age and gender and by considering familial relationships.  Single-SNP and haplotype association analyses included sex as a covariate and accounted for kinship using identity by state (genomic inflation, uncorrected data = 1.10).  Size was included in the model as either the actual wither height of the horse or using the genotype at loci previously associated with equine height.  Although no associations achieved genome-wide significance with this sample set, suggestive associations (FDR=0.1) were identified on chromosomes 4, 19, and 23 (p-values ~ 1.5x10^-5), including multiple SNPs in each region.  Additional samples, genotype and sequence data, are being collected to further investigate and identify candidate regions associated with Shivers in Clydesdales.