Fig. 4. Population structure and SNPs associate with disease manifestation.

A The first two principal components based on the 652 variants predicted to influence gene regulation or protein structure. Three clusters were supported using K-means clustering. Cluster names are based on Gerstein et al. ²⁰. Disease manifestation is indicated with a colored dot. Hypervirulent isolates (red) were significantly associated with ST93A (P = 0.0183), lethal CNS isolates (yellow) with ST93A (P = 0.0214), non-CNS isolates (blue) with ST93B-I (P = 0.0131), and latent isolates (purple) had a non-significant trend towards ST93A (P = 0.1353). Significance was determined using a two-sided Chi-squared test comparing expected versus observed values. B GWAS results for a trait (IFNγ) with multiple significant associations (Top Panel) and a trait with no statistically significant associatons (Calcofluor white, Bottom Panel). The ordinal categorical variables were analyzed with a proportional odds logistic mixed model and the quantitative variables were analyzed using a mixed linear model. Significant variants were identified by likelihood ratio test P values < 0.05 after a Bonferroni correction. Each dot represents a SNP, arranged by chromosome; significant SNPs are lableled with the gene name. C Venn diagram comparing the number of genes with significantly identified SNPs in the human GWAS²⁰, the ST93 all mouse GWAS, and the ST93A mouse GWAS. 14 genes overlapped across all three GWAS studies. D Significant SNPs from the ST93A GWAS are arranged by chromosome order and colored for significant variants. A lighter color indicates differences from the H99 genome associated with a decrease in the trait whereas a darker color indicates variants associated with an increase in that phenotype.