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Genome-wide association studies for canine hip dysplasia in single and multiple populations - implications and potential novel risk loci

Wang, Shizhi and Strandberg, Erling and Arvelius, Per and Clements, Dylan N. and Wiener, Pamela and Friedrich, Juliane (2021). Genome-wide association studies for canine hip dysplasia in single and multiple populations - implications and potential novel risk loci. BMC Genomics. 22 , 636
[Research article]

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Abstract

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 Federation 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.

Authors/Creators:Wang, Shizhi and Strandberg, Erling and Arvelius, Per and Clements, Dylan N. and Wiener, Pamela and Friedrich, Juliane
Title:Genome-wide association studies for canine hip dysplasia in single and multiple populations - implications and potential novel risk loci
Series Name/Journal:BMC Genomics
Year of publishing :2021
Volume:22
Article number:636
Number of Pages:12
Publisher:BMC
ISSN:1471-2164
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 402 Animal and Dairy Science > Animal and Dairy Science.
Keywords:German shepherd dogs, FCI grades, BVA, KC scores, QTL, Genetic diversity
URN:NBN:urn:nbn:se:slu:epsilon-p-113700
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-113700
Additional ID:
Type of IDID
DOI10.1186/s12864-021-07945-z
Web of Science (WoS)000694231500001
ID Code:25503
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:24 Sep 2021 14:25
Metadata Last Modified:24 Sep 2021 14:31

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