Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture
Fig 2
Linear mixed model GWAS corrects for population structure and identifies 99 ACL associated loci explaining a large proportion of phenotypic variance.
For each linear mixed model (LMM), the QQ plots show no evidence of population stratification relative to the expected distribution. Permutation testing with each model determined genome-wide significance at (a) P<3.63E-7 for GCTA (Genome-wide Complex Trait Analysis) [33], λ = 0.987 (b) P<6.097E-7 for GEMMA (Genome-wide Efficient Mixed Model Association) [34], λ = 0.994 and (c) P<4.01E-7 for PUMA (Penalized Unified Multiple-locus Association) [35], λ = 1.012. The plots represent analysis of 118,992 SNPs from 98 cases and 139 phenotype-negative controls. (d) With GCTA, 36 loci have P<5E-4, with the most significant locus located in CFA 24, which did not meet genome-wide significance defined by minimum p-values from permutation testing. (e) With GEMMA, 47 loci have P<5E-4, with the locus on CFA 24 meeting genome-wide significance defined by minimum p-values from permutation testing. (f) With PUMA, 65 loci were significant at P<5E-4 and the locus on CFA 24 exceeded genome-wide significance defined by minimum p-values from permutation testing. The single SNP that met genome-wide significance lies within the gene PPP1R16B.