Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies

Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP arrayplatform and updated reference genome. SNP arraysof this density are sufficient for detecting genetic associationswithin breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibriumrapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenceddogs and wolves, which increases the number of markers that can be queried in genome-wide association studiesapproximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibriumwith any single array marker. This reference panel resource will improve future genome-wide association studiesfor canine complex diseases and other phenotypes.