Mixed-model GWAS corrects for population structure and identifies 33 OSA associated loci explaining a large fraction of phenotype variance. In each breed, the QQ plots show no evidence of stratification relative to the expected distribution, identifying nominal significance at -log10p of 3.5 and the 95% empirically determined confidence intervals (dashed grey line) at -log10p of (a) 5 in the greyhounds, (b) 4 in the Rottweilers, and (c) 3.7 in IWH. In the IWH, a plateau of SNPs at P = 6.6 × 10-5 corresponds to a 1.65 Mb haplotype on chromosome 18 peaking at the gene GRB10. (d) In greyhounds, 14 loci have P<0.0005, with one locus, on chromosome 11, exceeding 95% confidence intervals (dashed lines). (e) In Rottweilers, 15 and 6 loci are identified, (f) while only four and two loci are identified in IWHs. (g) For each breed, the phenotype variance explained by the associated loci, broadly defined by SNPs with r2 >0.2 within 5 Mb of the peak SNP, exceeds 50%. In greyhounds, the 14 regions explain 56.9% +/− 12.5%, in Rottweilers, 15 regions explain 85.3 +/− 13.6%, and in IWH, four regions explain 53.1 +/− 15.5%. (h) For each affected dog (red circles) and unaffected dog (black circles), we estimated their relative risk based on the genotypes and odds ratio of the top SNP from each region for the breed (Table 1), showing that even using a small number of SNPs we see clear differences between the cases and the controls.
Karlsson et al. Genome Biology 2013 14:R132 doi:10.1186/gb-2013-14-12-r132