Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly 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 sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 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 disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes.
Bibliographical noteFunding Information:
This study was made possible with funding from Cornell University Center for Advanced Technology in Life Science Enterprise (NBS, RJT, ARB), NIH R01 GM103961 (ARB), The American Kennel Club grant CHF#02050 (KWS), NIH R24 GM082910-A1, The Morris Animal Foundation grant #D08CA-001 (SAC), and the Cornell University College of Veterinary Medicine. JJH was funded by a Next Generation Canine Fellowship from the Stanton Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.