A Study of 41 Canine Orthologues of Human Genes Involved in Monogenic Obesity Reveals Marker in the ADCY3 for Body Weight in Labrador Retrievers

SIMPLE SUMMARY: Obesity is a prevalent problem in dogs, although individual susceptibility is determined by a combination of genetic and non-genetic risk factors. This study looked at 41 canine orthologues of human genes linked to obesity in humans to find genes linked to weight in Labrador Retriever dogs. A linear mixed model using sex, age, and sterilization as covariates and population structure as a random effect were used to evaluate 11,520 variants in 50 adult dogs. A statistically significant variant in the ADCY3 gene was discovered throughout the study, making it a promising marker for canine obesity research. Our findings provide further evidence that the genetic makeup of obesity in Labrador Retriever dogs contains genes with large effect sizes. ABSTRACT: Obesity and overweight are common conditions in dogs, but individual susceptibility varies with numerous risk factors, including diet, age, sterilization, and gender. In addition to environmental and biological factors, genetic and epigenetic risk factors can influence predisposition to canine obesity, however, they remain unknown. Labrador Retrievers are one of the breeds that are prone to obesity. The purpose of this study was to analyse 41 canine orthologues of human genes linked to monogenic obesity in humans to identify genes associated with body weight in Labrador Retriever dogs. We analysed 11,520 variants from 50 dogs using a linear mixed model with sex, age, and sterilization as covariates and population structure as a random effect. Estimates obtained from the model were subjected to a maxT permutation procedure to adjust p-values for FWER < 0.05. Only the ADCY3 gene showed statistically significant association: TA>T deletion located at 17:19,222,459 in 1/20 intron (per allele effect of 5.56 kg, SE 0.018, p-value = 5.83 × 10(−5), TA/TA: 11 dogs; TA/T: 32 dogs; T/T: 7 dogs). Mutations in the ADCY3 gene have already been associated with obesity in mice and humans, making it a promising marker for canine obesity research. Our results provide further evidence that the genetic makeup of obesity in Labrador Retriever dogs contains genes with large effect sizes.