1,600 dogs shed new light on the genetic origins of canine hip dysplasia

Although common in large breed dogs such as Labrador retrievers and German shepherds, canine hip dysplasia (CHD)—the abnormal development and growth of a hip joint—can occur in dogs of any breed or size and can also lead to osteoarthritis. And while there’s no single cause of CHD, nutrition and genetics both play a major role.

Now, a new study out of Finland confirms previous research on the genetic side of the equation.

That previous research had identified dozens of genetic risk variants associated with CHD in different dog breeds, but the relevance of those variants to disease susceptibility remained unknown. The new study highlights the complex genetic architecture of canine hip dysplasia and validates more than 20 of those previously identified risk variants.

Corresponding author Antti Iivanainen, MD, PhD, and a team of researchers from the University of Helsinki reinvestigated those known risk variants using a large independent cohort of 1,600 dogs of 10 different breeds. The individual genetic variants were determined from blood samples.

The study validated 21 previously identified genetic regions—or loci—across 14 chromosomes associated with canine hip dysplasia; while 20 of those regions were associated with specific breeds, 1 was associated across all 10 breeds in the study.

The authors write that discovering the genetic basis of CHD is “one of the biggest veterinary conundrums in the past few decades.”

Inadequate sample sizes, the complexity and inaccuracy of the phenotypes, and an apparent genetic diversity across breeds have been issues in other studies. The sheer number of dogs in the new study helped mitigate some of those issues.

A significant finding: Genes related to a protein-modification process known as neddylation—a common mode of protein modification linked to activation or suppression of gene expression and encoded by the NEDD8 gene—were overrepresented among genes residing in the validated loci.

NEWStat reached out to Iivanainen to find out more.

NEWStat: Your team validated the disease association of 21 loci from 14 chromosomes. How was your research different from research done in the past?

Antti Iivanainen: Our study is a rare example of validating the associations using an independent cohort of animals.

NEWStat: What’s significant about the overrepresentation of genes associated with neddylation?

AI: Neddylation has not been associated with CHD before. Additional research is needed to confirm this finding and to investigate the mechanisms of how neddylation might be linked to the disease.

NEWStat: How did having a single cohort of 1,600 dogs impact your findings?

AI: Different associations have been found using different cohorts of animals. Also, in the present study, there were differences between breeds.

NEWStat: What’s the relationship between the loci of the genes underlying hip dysplasia and the actual genes?

AI: Association is determined statistically between a polymorphic marker in a specific locus and the disease. Often, there are genes near the marker that are not studied directly in this kind of study. These genes might, however, be directly causative to the disease, which would explain the statistical association between the marker gene and the disease.

NEWStat: How can your findings be of use to researchers going forward?

AI: The candidate genes and the validated loci should be the starting point of further studies aiming at uncovering mechanisms underlying the disease [to facilitate the development of new therapies and diagnostics].

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