GWAS Identification of Loci for Susceptibility to Recurrent Laryngeal Neuropathy in the Thoroughbred Horse

A healthy airway is of crucial importance to the equine athlete.  Recurrent Laryngeal Neuropathy (RLN) is a neurodegenerative condition that results in collapse of the larynx, obstruction of the airway and decreased performance.  Although several studies have suggested a genetic component to RLN, and several breeds are known to be particularly susceptible, the cause of this condition remains largely unknown.  In order to identify genetic loci contributing to this condition we have assessed disease status by endoscopic examination in 400 horses and tested for association with SNP markers from the Equine SNP70 genotyping array (Illumina Inc.).   Following correction for population stratification using EMMA, we identified a single locus on ECA3 significantly associated with RLN following Bonferroni correction (P= 1.08E-03, 44,775 SNPs, OR=2.309).   Yet the RLN associated region overlaps with a previously identified locus for body size and withers height in the horse.  While increased axonal length in a larger animal is a plausible risk factor for neurodegeneration, haplotype analysis suggests that the RLN causative mutation may be a unique change that is in tight LD with causative loci for size.  Additional work currently underway will genotype additional horses and hopefully disentangle these two loci, providing novel diagnostic and therapeutic options for RLN.