Study Finds Genetic Loci Associated With Anxiety and Aggression in Dogs: What Does It Mean for Kids?

Anxiety disorders are the most common type of mental illness in the United States. They are associated with increased risk of schizophrenia, depression, addiction and other psychiatric disorders. While much is known about the biochemistry of anxiety, there is very little known about the genetic variation associated with it.

Understanding the genetics of anxiety is critical information because it would explain why some people are more susceptible than others and reveal how predisposition interacts with environment influences, including social interactions and other stressors. It would also lead to new therapies.

However, it is technically difficult to identify genetic variation associated with human anxiety and other emotions. But, by exploiting the fact that such biology is highly conserved across species as far back as flies – and, most relevantly here, mammals – we have successfully completed the genome wide mapping of nine fear and aggression traits in dogs.

We predict that this information will be directly relevant to the same human traits, and our long-term goal is to identify therapeutic targets for emotional behavioral disorders. This could mean individualized treatments for children with anxiety disorders or the identification of biomarkers to monitor children with genetic risk.

Recently published in BMC Genomics, our findings reveal both distinct and shared genetic contributions to different social and non-social types of fear and aggression. For instance, we show that genetic predisposition to aggression toward an owner or a familiar dog is distinct from that for fear and aggression directed at unfamiliar humans and dogs. And some genetic variation is shared in fear and aggression behaviors. We reported 16 genome loci associated with these traits. Our strongest focus is on two genome regions associated with many types of canine fear and aggression. Fine mapping at those loci implicates genes that have not been reported to be associated with similar human behaviors, but which are biologically strong candidates. These genes are consistent with the core neural pathway of fear and aggression that encompases the amygdala to hypothalamic-pituitary-adrenal axis.

The most immediate implications are for veterinary behavioral medicine — genetic testing for risk of specific types of fear and aggression. Because these risk variants are common across dog breeds, the canine veterinary setting provides an ideal testbed for new therapies targeting those biochemical pathways.

Once it is determined which neuronal circuits are affected by the risk variation, this will likely reveal drug targets that could be inhibited or activated to increase or decrease the emotional behavioral effects. Those findings can immediately be tested in pet dog patients under owner consent. And, if those therapies are effective in dogs, they can then be applied to humans with similar conditions. Knowledge of the affected pathways will also provide biomarkers that can be used to identify the patients who are most likely to respond to such treatments.

This project has only just begun. We are continuing to identify and validate other genes associated with these traits. This work includes the expansion of dog breeds studied and biological validation of the findings.

These studies are led by Isain Zapata, PhD, in my lab and are made possible by the electronic cataloging of dog behavioral traits in the database C-BARQ by our collaborator James Serpell, PhD, and colleagues at the University of Pennsylvania, and by the generation of large genetic datasets by other groups in the United States and Europe.

Reference:

Zapata I, Serpell JA, Alvarez CE. Genetic mapping of canine fear and aggression. BMC Genomics. 8 Aug 2016. [Epub ahead of print]