Canxiety: Mapping New Loci for Canine Compulsion, Noise and Social Phobia

Dogs suffer from various anxiety traits including compulsive behavior, noise phobia and social phobia. Exaggerated, inappropriate and repetitive behaviour in animals is referred to as stereotypic or compulsive behaviour. Compulsive behaviour often onsets before the first year of life and includes various forms such as tail chasing (TC), light/shadow chasing, sucking, licking and chasing “invisible flies”. Noise sensitivity tends to develop later and affected dogs panic with loud noises such as thunders, fireworks and gunshots. Dogs that suffer from social phobia may adapt well with other dogs and new situations, but show a strong fear against unfamiliar persons. The potential causes of canine anxiety include both genetic and environmental factors. We have initiated an ambitious ERC-funded programme to investigate the clinical, genetic and environmental factors associated with various canine compulsions and phobias. Clinical studies include neurological studies combined with in vivo EEG measurements in selected dogs. We have also developed extensive and valitated online questionnaires to collect phenotypic information with possible environmental correlates. Questionnaires are targeted to a larger population of pet dogs to establish sufficient cohorts for successful genetic studies. We have also devised standardized behavioral experiments to correlate the external validity of the questionnaires. Our primary goal is to identify new genes and pathways in canine anxiety with a possible translation to corresponding human traits. We have established one of the largest dog DNA banks in the world with 50 000 samples from 300 breeds, including thousands of dogs with particular anxieties. Our in vivo EEG data suggests that compulsions are not focal seizures. Questionnaire data has defined significant case control cohorts with extreme phenotypes in each trait and identified several related environmental factors such as socalization in the puppyhood and maternal care. Finally, genetic association studies with canine HD SNP arrays have revealed new genome widely significant loci, suggesting a strong genetic contribution in each trait as proposed by the pedigrees. These results demonstrate the power of the dog breeds to unravel new anxiety loci in carefully phenotyped study cohorts. Ongoing resequencing and transcriptome studies are expected to identify novel risk haplotypes, causative variants and affected pathways for further validation experiments. Gene discoveries would establish the breeds as important therapeutic models, improve our understanding of the affected molecular pathways in anxiety, provide new candidate genes for human medicine and improve canine breeding plans to reduce the incidence of the traits in the affected breeds.