A Genome Wide Association of Size Variation in Horses Reveals a Novel Candidate Locus Affecting Size Variation in Horses

Using the Illumina 54K SNP chip, we genotyped 48 horses from 16 breeds that represented extremes in body size. Identifying QTLs affecting height variation is important to understand the genetic architecture and morphologic changes undergone during domestication. We performed a GWAS for withers height in the 48 animals where we successfully accounted for the population structure in our data with a mixed model approach in EMMA using an additive, recessive and dominant model of inheritance. Population stratification in this diverse dataset was extreme, producing a genome wide inflation factor of 2.43. Using EMMA, we were able to reduce the inflation factor to 1.19. Our dominant model GWAS detected two novel significant QTLs at chromosomes 1 and 19. The most significant hit was on chromosome 1 near the ANKRD1 gene. ANKRD1 encodes the Ankyrin Repeat Domain-Containing Protein 1, a protein that is involved in the transforming growth factor (TGF)-β pathway and is up-regulated in response to atrophy induced bone loss. The marker SNP explained 1.875 inches of withers height (corresponding to 6 % of total height in these animals) variation when genotyped in a new sample set of 36 unrelated ponies. We intend to further verify our results by increasing the sample size in this single-breed population. Investigation of the functional role that this gene plays in determining withers height in horses and detection of the putative causative mutation is ongoing.