O'Grady John F, McHugo Gillian P, Ward James A, Hall Thomas J, Faherty O'Donnell Sarah L, Correia Carolina N, Browne John A, McDonald Michael, Gormley Eamonn, Riggio Valentina, Prendergast James G D, Clark Emily L, Pausch Hubert, Meade Kieran G, Gormley Isobel C, Gordon Stephen V, MacHugh David E
UCD School of Agriculture and Food Science, University College Dublin, Belfield, Ireland.
Irish Blood Transfusion Service, National Blood Centre, James's Street, Dublin, Ireland.
Commun Biol. 2025 Mar 24;8(1):479. doi: 10.1038/s42003-025-07846-x.
Mycobacterium bovis 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. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.
牛分枝杆菌可引发牛结核病（bTB），这是一种牛的传染病，对人类构成人畜共患病威胁。研究表明，在bTB疾病期间外周血（PB）转录组会受到干扰，但支撑这种转录反应的基因组结构仍知之甚少。在此，我们分析了来自63只对照动物和60只确诊感染牛分枝杆菌动物的PB转录组学数据，检测到2592个差异表达基因，这些基因扰乱了多种免疫反应途径。利用估算的全基因组SNP数据，我们对数千个顺式表达数量性状位点（eQTL）进行了表征，并表明在牛分枝杆菌感染期间，PB转录组受到群体内基因组变异的显著影响。将我们的顺式eQTL数据与bTB易感性全基因组关联研究（GWAS）汇总统计数据相结合，我们进行了全转录组关联研究，鉴定出115个功能相关基因（包括RGS10、GBP4、TREML2和RELT），并提供了重要的新组学数据，以帮助理解宿主对导致哺乳动物结核病的分枝杆菌感染的反应。
