AmylaseALTGenotypesGenotypes of dogs in the study at SNPs most highly associated with Amylase activity and ALT activity.cbc_dogsIdentification numbers of dogs for which Complete Blood Count data was included in the study.cbc_genos.bedBed file used in GWAS for CBC phenotypes.cbc_genos.bimBim file used in GWAS for CBC phenotypes.cbc_genos.famfam file used in GWAS for CBC phenotypes.ccp_dogsIdentification numbers of dogs for which Clinical Chemistry data was included in the study.ccp_genos.bedBed file used in GWAS for CCP phenotypes.ccp_genos.bimBim file used in GWAS for CCP phenotypes.ccp_genos.famFam file used in GWAS for CCP phenotypes.cbc_residResidual values for Complete Blood Count phenotypes from linear model after correcting for age, sex and spay/neuter status, and body weight covariates.ccp_residResidual values for Clinical Chemistry Profile phenotypes from linear model after correcting for age, sex and spay/neuter status, and body weight covariates.CCPSickDogsRaw data from Clinical Chemistry Profile of dogs with diagnosed or presumed liver disease/injury.CBCCCPValuesByBreedWithPlinkBasedMAFSelect Complete Blood Count and Clinical Chemistry values averaged by dog with breed information, breed name abbreviation, count of dogs per breed from which mean (healthy) ALT value was calculated, mean allele frequency for the SNP most highly associated with ALT activity per breed in our database (see manuscript for further explanation). Data used in Figure 3 of manuscript.CCPValuesGenoAveragedByDogClinical Chemistry phenotype data averaged by dog for 335 dogs selected as clinically healthy with genotype data for ALT activity and Amylase activity.PhenotypeKeyCBCResidKey for column names for CBC Residual text file.PhenotypeKeyCCPResidKey for column names for CCP Residual text file.PlinkBreedFreqForALTAssocSNPList of breeds shown in figure 3 along with number of chromosomes (column 2 ) and number of dogs (column 3) on which mean allele frequency for breed was based.

Since the publication of the dog genome and the construction of high-quality genome- wide SNP arrays, thousands of dogs have been genotyped for disease studies. For many of these dogs, additional clinical phenotypes are available, such as hematological and clinical chemistry results collected during routine veterinary care. Little is known about the genetic basis of variation in blood phenotypes, but this variation may play an important role in the etiology and progression of many diseases. From a cohort of dogs that had been previously genotyped on a semi-custom Illumina CanineHD array for various genome-wide association studies (GWAS) at Cornell University Hospital for Animals, we chose 353 clinically healthy, adult dogs for our analysis of clinical pathologic test results (14 hematological tests and 25 clinical chemistry tests). After correcting for age, body weight and sex, genetic associations were identified for amylase, segmented neutrophils, urea nitrogen, glucose, and mean corpuscular hemoglobin. Additionally, a strong genetic association (P = 8.1×10-13) was evident between a region of canine chromosome 13 (CFA13) and alanine aminotransferase (ALT), explaining 23% of the variation in ALT levels. This region of CFA13 encompasses the GPT gene that encodes the transferase. Dogs homozygous for the derived allele exhibit lower ALT activity, making increased ALT activity a less useful marker of hepatic injury in these individuals. Overall, these associations provide a roadmap for identifying causal variants that could improve interpretation of clinical blood tests and understanding of genetic risk factors associated with diseases such as canine diabetes and anemia, and demonstrate the utility of holistic phenotyping of dogs genotyped for disease mapping studies.