Genome-wide association mapping has uncovered dog fear and aggression gene variants that may have been involved in dog domestication. These variants could guide studies of dog behavioral problems and even yield insights into human anxiety disorders. [Josh Plueger/U.S. Air Force]
Genome-wide association mapping has uncovered dog fear and aggression gene variants that may have been involved in dog domestication. These variants could guide studies of dog behavioral problems and even yield insights into human anxiety disorders. [Josh Plueger/U.S. Air Force]

Some dogs snarl and snap at anyone—familiar people, even their owners. Other dogs display aggression more selectively, directing it toward strangers, people, or dogs that happen to be unfamiliar. Curiously, the snarlier dogs and the relatively subdued dogs tend to be genetically distinct. Approximately one dozen genes have variants that are associated with sociability, or with fear and aggression.

The gene variants were uncovered by researchers based at Nationwide Children’s Hospital. According to these researchers, reduced-fear gene variants may have been involved in the domestication process. The researchers also assert that their findings are relevant not only to dog behavioral problems, but also to human anxiety disorders.

The new findings appeared August 8 in the journal BMC Genetics, in an article entitled, “Genetic Mapping of Canine Fear and Aggression.” In the near term, the findings could inform genetic tests that would reveal the risk of specific types of fear and aggression in dogs. In the long term, the findings could shed light on human anxiety disorders and aggression, violence, and criminality.

“We conducted genome-wide association (GWA) mapping of breed stereotypes for many fear and aggression traits across several hundred dogs from diverse breeds,” wrote the article’s authors. “We confirmed those findings using GWA in a second cohort of partially overlapping breeds. Lastly, we used the validated loci to create a model that effectively predicted fear and aggression stereotypes in a third group of dog breeds that were not involved in the mapping studies.”

The researchers found that known loci variants (IGF1 and HMGA2) for small body size are associated with separation anxiety, touch sensitivity, owner-directed aggression, and dog rivalry. The researchers also notice that two other loci (between GNAT3 and CD36 on chromosome 18, and near IGSF1 on the X chromosome) are associated with several traits, including touch sensitivity, nonsocial fear, and fear and aggression that are directed toward unfamiliar dogs and humans.

“Our strongest focus is on specific genes related to aggression toward unfamiliar humans and dogs, which are associated with highly relevant genes at two genome regions,” said Carlos Alvarez, Ph.D., principal investigator in the Center for Molecular and Human Genetics in The Research Institute at Nationwide Children's Hospital. “Those genes are consistent with the core fear and aggression neural pathway known as the amygdala to hypothalamic–pituitary–adrenal axis.”

Because these risk variants are common across dog breeds, the canine veterinary setting provides an ideal test bed 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,” noted Dr. Alvarez. “We are continuing to identify and validate other genes associated with these traits, including the expansion of dog breeds studied and biological validation of the findings. We are excited about what this work will continue to uncover.”








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