Heritability and complex segregation analysis of diabetes mellitus in American Eskimo Dogs

Abstract Background Heritability and mode of inheritance of spontaneous diabetes mellitus (DM) in American Eskimo Dogs (AED) are unknown. Objective Investigate the heritability and mode of inheritance of DM in AED. Animals An extended family of AED including 71 AED without DM, 47 AED with an unknown phenotype, and 38 AED with spontaneous DM. Methods Retrospective evaluation of inheritance. A logistic regression model was formulated to evaluate the heritability of DM, including effects of sex and neuter status. Subsequently, complex segregation analysis was employed to investigate the inheritance pattern of DM in AED. Six plausible models were considered, and the Akaike Information Criterion was used to determine the best of the biologically feasible models of inheritance of DM in AED. Results Heritability of DM in AED is estimated at 0.62 (95% posterior interval 0.01‐0.99). Predicted DM probabilities for neutered females (NF), intact females (IF), neutered males (NM), and intact males (IM) were 0.76, 0.11, 0.63, and 0.12, respectively. There was no overlap between the 95% posterior intervals of disease probabilities in NF and IF or in NF and IM. Complex segregation analysis suggested that the mode of inheritance of DM in AED is polygenic, with no evidence for a single gene of large effect. Conclusions and Clinical Importance The estimated heritability of DM in AED is high but has low precision. Diabetes mellitus transmission in AED appears to follow a polygenic inheritance. Breeders could successfully implement a breeding program to decrease the incidence of DM in AED.