Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation

Abstract

Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene. Here we set out to investigate whether DNA methylation within the OXTR promoter region of pet dogs is linked to their owner’s interaction style and to the social behavior of the dogs. To be able to do so, we collected buccal epithelial cells and, in Study 1, we used pyrosequencing techniques to look for differentially methylated CpG sites in the canine OXTR promoter region on a heterogeneous sample of dogs and wolves of different ages and keeping conditions. Four identified sites (at positions -727, -751, -1371, and -1383 from transcription start site) showing more than 10% methylation variation were then, in Study 2, measured in triplicate in 217 pet Border Collies previously tested for reactions to an adverse social situation (i.e., approach by a threatening human) and with available data on their owners’ interaction styles. We found that CpG methylation was significantly associated with the behavior of the dogs, in particular with the likelihood that dogs would hide behind their owner or remain passive when approached by a threatening human. On the other hand, CpG methylation was not related to the owners’ behavior but to dog sex (at position -1371). Our findings underpin the complex relationship between epigenetics and behavior and highlight the importance of including epigenetic methods in the analysis of dog behavioral development. Further research is needed to investigate which environmental factors influence the epigenetic variation of the OXTR gene.

Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders

“…Epigenetic studies in humans have found altered DNA methylation in the 5′ CpG island of OXTR in a wide spectrum of morbid behaviors and neuropsychiatric disorders, such as autism spectrum disorder (ASD), schizophrenia, bipolar, depression, obsessive-compulsive disorders (OCD), and anxiety (12)(13)(14)(15)(16)(17)(18). Similar correlations between DNA methylation and behavior are also reported in other species, such as dog and nonhuman primates (19,20).…”

The effect of oxytocin on human-directed social behaviour in dogs (Canis familiaris)

“…While evidence has already been found that dogs behaving differently have different methylation levels (Cimarelli et al, 2017), it is yet to be examined how these different methylation levels emerge as a result of environmental influence, as for example no effect of owner interaction style on methylation levels was found.…”

“…Another study from the same group analysed buccal samples of nine dogs (from six different breeds and three mixed breeds) and three timber wolves (Cimarelli et al, 2017) Weak gender-specific associations with methylation level. Female dogs had higher methylation levels than males in position −1371, males had higher methylation levels than females in position −727.…”

Dog behaviour : Intricate picture of genetics, epigenetics, and human-dog relations

“…This is a new area of research, and studies on dog behaviour and epigenetic factors are scarce. As the first of its kind, Cimarelli, et al (180) could associate dog's social behaviour to DNA methylation of the oxytocin receptor gene. In males, a lower methylation level was associated with approaching a threatening stranger and a higher level with hiding behind their owner.…”

“…Interestingly, Cimarelli, et al (180) also tested if owner interaction style affects methylation of dog's oxytocin receptor gene. They did not find an association between the two.…”