Dog Aggression Toward Owner Can Be Due to Genetic Predisposition

Everyone experiences some type of anxiety on occasion, but for the most part, it’s fleeting; the feeling comes and goes. For others, the feeling does not go away, instead, it worsens as time goes by: this is an anxiety disorder. According to a Nationwide Children’s Hospital press release, in the United States, anxiety disorders are the most common kind of mental illness. Although much research has been done in the realm of anxiety’s biochemistry, much remains unknown about the role that genetic may play.

Researchers at the Nationwide Children’s Hospital report in a study that was recently published in BMC Genomics, that “man’s best friend” has a genetic predisposition to aggression directed towards an owner or a familiar dog. Additionally, this fear and aggression is not the same as when those feelings are directed toward unfamiliar dogs and humans. Twelve genes are associated with these traits, according to the press release.

Carlos Alvarez, PhD, principal investigator in the Center for Molecular and Human Genetics in The Research Institute at Nationwide Children’s Hospital, said “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. Those genes are consistent with the core fear and aggression neural pathway known as the amygdala to hypothalamic-pituitary-adrenal-axis.”

The study conducted by Alvarez and his team aimed to better understand fear and aggression. The team was able to map behavioral traits by using breed stereotypes in order to conduct a series of interbreed genome scans. In order to ensure the validity of their findings, the researchers conducted their study in two phases: discovery and validation. In the first phase, the researchers used nine behavioral phenotypes for fear and aggression to analyze two SNP datasets, according to the study. Then, the researchers set out to validate their findings by predicting behavior for breeds that were not included in the study’s first phase. The researchers hypothesized that they would be able to predict certain behavioral traits based on a few markers.

The discovery data that the team of researchers used was what they refer to as “C-BARQ phenotypes” which are behavioral phenotypes that include “values and distributions for aggression and fear variables” that had previously been published for the 30 “most popular breeds” of the American Kennel Club. The data consisted of a collection of behavior information of dogs that were registered with the American Kennel Club that had been reported by the owners; 6,818 animal subjects were used to compose this set of data.

According to the study, “C-BARQ data decomposes aggression into 4 classes: stranger-directed aggression (towards unfamiliar humans), dog-directed aggression (toward unfamiliar dogs), owner-directed aggression and dog rivalry (towards familiar humans and dogs respectively). In a similar way C-BARQ decomposes fear into 5 classes: stranger-oriented fear (towards unfamiliar humans), dog-oriented fear (towards unfamiliar dogs), nonsocial fear (towards environmental phenomena), separation-related anxiety (being left alone by the owner) and touch sensitivity.” Dog rivalry and touch sensitivity was previously validated using 200 dog subjects that had previously been diagnosed with behavior problems.

The researchers then mapped out and made predictions based on markers that had been detected for breeds from what they refer to as the “Vaysse dataset,” one of the two datasets used in the study. The Vaysse dataset contained 456 subjects that represented 30 dog breeds as well as around 175,000 “SNPs on the CanineHD array.” The other dataset, referred to as the “Bokyo dataset,” contained 890 subjects that represented 80 dog breeds as well as around 45,000 “SNPs on the Affymetrix v.2 Canine array.” However, the stereotypic phenotypes were not available for all of the breeds that were in both datasets, and so the researchers only used the subjects that had the stereotypic phenotypes, which resulted in 150 subjects from 11 dog breeds, used in both datasets.

After mapping out the breed stereotypic phenotypes for fear and aggression traits and confirming them using a second cohort from the Bokyo dataset, the researchers set out to create a model that would successfully predict fear and aggression using “validated loci” in a third group of dog breeds that were not involved in the previous cohorts.

They found that “i) known IGF1 and HMGA2 loci variants from small body size are associated with separation anxiety, touch-sensitivity, owner directed aggression and dog rivalry; and ii) two loci, between GNAT3 and CD36 on chr18, and near IGSF1 on chrX, are associated with several traits, including touch-sensitivity, non-social fear, and fear and aggression that are directed toward unfamiliar dogs and humans,” according to the study.

Dr. Alvarez feels that these findings are not only important when it comes to understanding behavioral issues in dogs, but they can also be relevant to anxiety disorders in humans, according to the press release. The veterinary setting is an ideal place to test out new therapies that target biochemical pathways related to anxiety, due to the fact that there are common risk variants across dog breeds. If researchers can distinguish which neuronal circuits risk variation affects then this could potentially reveal new targets for drugs developed to influence emotional behavioral effects. The next step would be to take the results of these findings, and with the consent of the owners, test developed therapies in dogs. The researchers hope that if the tests are successful, humans could eventually benefit from the same kind of therapies.

According to the press release, the additional knowledge about the biochemical pathways will provide researchers with biomarkers that could assist in the identification of patients that would be most responsive to such treatments.

When speaking of the future, Dr. Alvarez said, “This project has only just begun. 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.”