Principal component analysis of canine hip dysplasia phenotypes and their statistical power for genome-wide association mapping

摘要

The aims of this study were to undertake principal component analysis (PCA) of hip dysplasia (HD) and to examine the power of the principal components (PCs) in genome-wide association studies. A cohort of 278 dogs for PCA and that of 369 dogs for genotyping were used. The distraction index (DI), the dorsolateral subluxation (DLS) score, the Norberg angle (NA), and the extended-hip radiographic (EHR) score were used for the PCA. One thousand single-nucleotide polymorphisms (SNPs) (of 23,500) were used to simulate genetic locus sharing between the HD phenotypes and 1000 SNPs were used to calculate the genetic mapping power of the PCs. The DI and the DLS score (first group) reflected hip laxity and the NA and the EHR score (second group) reflected the congruency between the femoral head and acetabulum. The average hip measurements of the two groups reflected in the first PC captured 55% of total radiographic variation. The first four PCs captured 90% of the total variation. The PCs had higher statistical mapping power to detect pleiotropic quantitative trait loci (QTL) than the raw phenotypes. The PCA demonstrated for the first time that HD can be reduced mathematically into simpler components essential for its genetic dissection. Genes that contribute jointly to all four radiographic hip phenotypes can be detected by mapping their first four PCs, while those contributing to individual phenotypes can be mapped by association with the individual raw phenotype.