Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

<p><em><span>Mycobacterium bovis</span></em><span> causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood.</span>&nbsp;Here, we analyse PB transcriptomics data from 63 control and 60 confirmed <em>M. bovis </em>infected animals and detect 2,592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of <em>cis&shy;</em>-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during <em>M. bovis</em> infection. Integrating our <em>cis-</em>eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 132 functionally relevant genes (including <em>RGS10</em>, <em>GBP4</em>, <em>TREML2</em>, and <em>RELT</em>) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.</p> <p>&nbsp;</p>