UK dogs data from: Genome-wide association studies for canine hip dysplasia in single and multiple populations – implications and potential novel risk loci

Background: Association mapping studies of quantitative trait
loci (QTL) for canine hip dysplasia (CHD) can contribute to the
understanding of the genetic background of this common and debilitating
disease and might contribute to its genetic improvement. The power of
association studies for CHD is limited by relatively small sample numbers
for CHD records within countries, suggesting potential benefits of joining
data across countries. However, this is complicated due to the use of
different scoring systems across countries. In this study, we incorporated
routinely assessed CHD records and genotype data of German Shepherd dogs
from two countries (UK and Sweden) to perform genome-wide association
studies (GWAS) within populations using different variations of CHD
phenotypes. As phenotypes, dogs were either classified into cases and
controls based on the Fédération Cynologique Internationale (FCI)
five-level grading of the worst hip or the FCI grade was treated as an
ordinal trait. In a subsequent meta-analysis, we added publicly available
data from a Finnish population and performed the GWAS across all
populations. Genetic associations for the CHD phenotypes were evaluated in
a linear mixed model using 62,089 SNPs. Results: Multiple SNPs
with genome-wide significant and suggestive associations were detected in
single-population GWAS and the meta-analysis. Few of these SNPs overlapped
between populations or between single-population GWAS and the
meta-analysis, suggesting that many CHD-related QTL are
population-specific. More significant or suggestive SNPs were identified
when FCI grades were used as phenotypes in comparison to the case-control
approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional
candidate genes associated with hip dysplasia. Conclusions: Our
findings confirm the complex genetic nature of hip dysplasia in dogs, with
multiple loci associated with the trait, most of which are
population-specific. Routinely assessed CHD information collected across
countries provide an opportunity to increase sample sizes and statistical
power for association studies. While the lack of standardisation of CHD
assessment schemes across countries poses a challenge, we showed that
conversion of traits can be utilised to overcome this obstacle.