Fig. 1: Human-to-Mtb genome-wide association study in 1556 tuberculosis patients.

a Study design schematic. We obtained DNA from 1556 Peruvian individuals with TB disease and cultured pathogens to perform host genotyping and Mtb WGS. The genotype of each common Mtb variant was considered as the response variable (Y: 0 or 1), and the genotype of each host variant was the independent variable (X: 0, 1 or 2), resulting in one test per host SNP-Mtb SNP pair. b Grid plot summarizing the genome-to-genome analysis. The x-axis denotes position within the human genome with alternating colors (white and light gray) for each chromosome. The y-axis denotes position within the Mtb genome. Point colors represent the association p-value (-log₁₀(P)) from the mixed effect logistic regression. The most significant host-Mtb pair association is indicated. Six randomly chosen Mtb variants in tight linkage (Pearson r² > 0.8) with position 271640 are shown in light blue, indicating that the same human variant rs3130660 is significantly associated with multiple Mtb positions. c Manhattan plot of the GWAS analysis when treating genotypes of Mtb position 271640 as the outcome. The x-axis indicates genomic location, where as the y-axis shows the (-log₁₀(P)) from mixed effect logistic regression model (d) A maximum likelihood phylogenetic tree inferred from 13,981 variants of 1,555 Peruvian Mtb isolates (excluding one Lineage 1 sample for visualization purposes). Branch colors represent the inferred lineages. Filled squares on the right indicate the presence (red) or absence (gray) of the six Mtb variants identified in the g2g analysis and highlighted in (b) Source data for (a).-c are provided in the Source Data 1 file. Source data for (d) are provided in Source Data 2 file.