Interpreting Breed-Specific Risk of Genetic Disease

Most health outcomes in dogs and humans are caused by a combination of environmental and genetic factors.

Environmental factors include both our physical environment, like climate and chemical exposures, and elements of our lifestyle, like diet and exercise. At the Dog Aging Project we collect information about environmental factors through the Health and Life Experience Survey and through publicly available measures of environmental quality.

Genetic variations can influence risk of health outcomes either positively or negatively. For instance, some genetic variations can be protective and therefore decrease the risk of a particular disease or health outcome from occurring. Other genetic variations can increase an individual’s risk of experiencing a particular disease or health outcome. One example from human medicine is the association between BRCA2 mutation and risk of breast cancer.

Studying the genetic influence on health outcomes in dogs does not always require us to know all the details about an individual dog’s genetic variations. This is because the genetic variations within a particular breed of dog tend to be relatively similar across all dogs within the breed. Thus, we can use dog breeds as a surrogate for individual genetic information.

Previous research in dog populations has shown that dog breeds have different levels of risks associated with different health and disease outcomes. For example, Bernese Mountain Dogs have been shown to be 225 times more likely than other breeds to be affected with a type of cancer called malignant histiocytosis. This means that an individual dog from a breed, like Bernese Mountain Dogs, which is known to have an increased risk of developing a certain disease, is more likely to have the genetic variation associated with the disease outcomes than are individual dogs from a different breed.

However, this doesn’t mean that all (or even most) individual dogs in that breed will develop that specific disease. When we talk about breed-related risks of disease, we are talking about the entire breed as a whole, not about individual dogs. Using the human example again, not all women who have the BRCA2 mutation will get breast cancer.

Another aspect of risk that is worth considering is the epidemiological concept of attributable risk. Consider this hypothetical example: Blue dogs are 4 times more likely to have crooked tails than red dogs. Four times greater risk is a big deal, right? That means there is a 400% greater chance that the blue dog will develop a crooked tail than the red dog will.

However, the magnitude of the increased risk depends on what the underlying risk of developing a crooked tail in red dogs was in the first place. If it was a very, very low risk before, increasing that risk 4 times still means it’s a really, really low risk. We call the difference between the underlying risk and the increased level of risk “attributable risk.”

To continue with this example, let’s say that red dogs have a risk of developing a crooked tail that is 1 in a 1,000,000. That means that blue dogs have a risk of developing a crooked tail that is 4 in 1,000,000. So, though the risk for blue dogs is increased four-fold, the absolute increase – or attributable risk – is 3 in a million, which is still a really small risk.

That doesn’t mean that breed-specific risks of disease have no significance for an individual dog though. Breed-specific risk can help you and your veterinarian determine if there are specific precautions you could take. It might be possible to modify environmental factors that may contribute to the same negative outcome your dog might be at increased genetic risk for developing. For instance, if your dog’s breed is at increased risk of developing obesity, your veterinarian may recommend a diet and exercise regimen that will help to reduce the risk of this health outcome.

Another way that breed predispositions may influence your dog’s care is that you may choose to take proactive measures to detect the health outcome early if it were to occur. This is similar to the precautions that are taken in human populations where there is a known familial risk of a disease outcome, like the BRCA2 mutation mentioned previously. Using that example, women who have the BRCA2 mutation are advised to have regular breast exams in order to detect any changes early so that they can receive treatment before the disease has time to progress. The same is true for dogs.

Genetic research, like the work we are doing at the Dog Aging Project, has the potential to lead to new diagnostic, preventative, and treatment approaches. The hope is that these approaches can be personalized for dogs (and humans!) with specific genotypes so that we can extend the healthy period of life (also called healthspan) for all of us!