Genome-wide association analysis of idiopathic epilepsy in the Belgian shepherd

BACKGROUND: Idiopathic epilepsy (IE) is a common neurological disorder in the domestic dog, and is defined as repeated seizure activity having no identifiable underlying cause. Some breeds, such as the Belgian shepherd dog, have a greater prevalence of the disorder. Previous studies in this and other breeds have identified ADAM23 as a gene that confers risk of IE, although additional loci are known to exist. The present study sought to identify additional loci that influence IE in the Belgian shepherd dog. RESULTS: Genome-wide association studies (GWAS) revealed a significant association between IE and CFA 14 (p < 1.03 E(− 08)) and a suggestive association on CFA 37 (p < 2.91 E(− 06)) in a region in linkage disequilibrium with ADAM23. Logistic regression identified a 2-loci model that demonstrated interaction between the two chromosomal regions that when combined predicted IE risk with high sensitivity. CONCLUSIONS: Two interacting loci, one each on CFAs 14 and 37, predictive of IE in the Belgian shepherd were identified. The loci are adjacent to potential candidate genes associated with neurological function. Further exploration of the region is warranted to identify causal variants underlying the association. Additionally, although the two loci were very good at predicting IE, they failed to capture all the risk, indicating additional loci or incomplete penetrance are also likely contributing to IE expression in the Belgian shepherd dog.