Abstract: Background- A range of genetic factors contribute to cognitive health in people, but the genetic influences on cognition in dogs have not been characterized. Hypothesis/Objectives- Identify genetic loci associated with cognitive health assessed by the DISHAA tool in mature Golden Retrievers. Animals- Client-owned Golden Retrievers enrolled in the Golden Retriever Lifetime Study were evaluated at 6–11 years of age and had a completed DISHAA questionnaire with single-nucleotide polymorphism (SNP) data (n = 1,126). Methods- The DISHAA was used to determine cognitive health. SNP data were available from the Axiom array. Quality control was performed, followed by SNP filtering for minor allele frequency ≥1% and Hardy–Weinberg equilibrium. Linkage disequilibrium–based principal components were used to control for population structure, and stepwise-regression identified optimal covariates. Dogs with intracranial lesions were excluded. A genome-wide efficient mixed-model analysis was performed, followed by linkage disequilibrium analysis and evaluation of phenotype-wide associations. Results- After exclusions, there were 1123 dogs available for analysis. The majority of dogs had normal DISHAA scores (median: 1, range: 0-27), but a subset had a higher score associated with mild or moderate cognitive dysfunction (n=239, median: 5). A significant locus was identified on chromosome 20 (49.5 to 55.6 megabases). Intercellular adhesion molecule (ICAM) genes were located at the center of this region. These genes overlap with human phenome-wide associations involving neuroticism, memory, and conscientiousness. Conclusions and Clinical Importance- These findings suggest shared genetic mechanisms underlying cognitive health in dogs and people.
