DOI: 10.5061/dryad.h44j0zpkf
title: UK dogs data from: Genome-wide association studies for canine hip dysplasia in single and multiple populations – implications and potential novel risk loci

description: 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.
description: DNA was
 extracted from saliva samples collected with Performagene PG-100 swabs (UK
 dogs). The dogs were genotyped using the Illumina CanineHD Whole-Genome Genotyping BeadChip featuring 172,115 SNPs. For quality control, filtering was imposed in GenomeStudio version 2.0 for sample call rate &gt; 90%, SNP call rate &gt; 98%, reproducibility (GTS) &gt; 0.6 and low or confounded signal characterised by AB R mean (mean normalized intensity of the AB cluster) &gt; 0.3. SNPs were also filtered using PLINK version 1.9 (27,28) to remove those with minor allele frequency (MAF) &lt; 0.05 and significant deviations from Hardy-Weinberg equilibrium (HWE) (Bonferroni-corrected p-value of 0.05 = 4.5 x 10-7), resulting in 78,088 autosomal SNPs. Canine hip dysplasia records for genotyped UK dogs were provided by the British Kennel Club (KC): the hip status of the dogs was screened by the BVA/KC scheme. In this scheme, determined by the severity of HD-related measurements from normal to severe, aggregated scores for bilateral joints (total hip score; HS) are given from 0 to 106 (0 to 53 for each joint). BVA/KC total hip scores for UK dogs were also converted into FCI five-level grades following a recommended conversion (0-10=A, 11-25=B, 26-35=C, 36-50=D, 51-106=E). As third phenotype approach, UK dogs were grouped into "cases" (BVA/KC scores &gt;=11) and "controls" (scores 0-10).
description: Information on the data sets can be found in the
 "README.txt" file.