Researchers Report First Validated Canine Behavioral Genetics Findings of Nine Fear and Aggression Traits in Dogs

August 10, 2016

Anxiety disorders are the most common type of mental illness in the United States. And while much is understood about the biochemistry of anxiety, little is known about the genetic variation associated with it.
 
Recently published in BMC Genomics, a study led by researchers at Nationwide Children's Hospital reports 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. The researchers identified approximately 12 genes associated with these traits. 
 
“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, PhD, 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.” 
 
The findings not only relate to the most important dog behavioral problems but are also likely to be highly relevant to human anxiety disorders, according to Dr. Alvarez. 
 
While the most immediate implications are for veterinary behavioral medicine — genetic testing for risk of specific types of fear and aggression, the long term implications for adults and children with anxiety disorders are encouraging. 
 
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,” said 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.”
 
The studies were led by Dr. Isain Zapata in Dr. Alvarez’s Lab in the Center for Molecular and Human Genetics in The Research Institute at Nationwide Children’s Hospital. These studies are made possible by the electronic cataloging of dog behavioral traits in the database C-BARQ by 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.

About Nationwide Children's Hospital

Named to the Top 10 Honor Roll on U.S. News & World Report’s 2024-25 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit free-standing pediatric health care systems providing unique expertise in pediatric population health, behavioral health, genomics and health equity as the next frontiers in pediatric medicine, leading to best outcomes for the health of the whole child. Integrated clinical and research programs, as well as prioritizing quality and safety, are part of what allows Nationwide Children’s to advance its unique model of care. Nationwide Children’s has a staff of more than 16,000 that provides state-of-the-art wellness, preventive and rehabilitative care and diagnostic treatment during more than 1.8 million patient visits annually. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s physicians train the next generation of pediatricians and pediatric specialists. The Abigail Wexner Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded free-standing pediatric research facilities. More information is available at NationwideChildrens.org