Common genetic determinants of dynamic human in vivo immune response to Mycobacterium tuberculosis.
Zhang, P.; Turner, C. T.; Chandran, A.; Parks, T.; Rosenheim, J.; Jiang, J.; Bell, L. C.; Rose-Key, R.; Berkeley, M.; Capocci, S.; Lipman, M.; Kunst, H.; Lozewicz, S.; Tomlinson, G. S.; Knight, J. C.; Noursadeghi, M.
Show abstract
We investigated host-genetic TB susceptibility by expression quantitative trait loci (eQTL) analysis of the tuberculin skin test (TST) as a standardised challenge model of human in vivo TB immunology. Paired genotyping with 415 RNA-sequencing profiles from day 2 and day 7 TST biopsies in 267 individuals with latent or active TB identified cis-eQTLs affecting 1,719 response genes. The strongest signal mapped to ERAP2, and colocalisation analysis linked reduced ERAP2 expression to increased TB risk in GWAS data. Heritability was greatest in HLA class II antigen presentation and T-cell activation pathways. HLA-DR haplotypes associated with subsequent expansion of Mtb-reactive T cells, linking host genotype to antigen-specific immunity. Trans-eQTLs also identified a proliferative programme centred on NCAPD3, implicating genetically regulated cell-cycle control as an antigen-independent determinant of T-cell immunity. These findings provide a functional framework for interpreting TB susceptibility loci and identification of candidate biomarkers for TB risk stratification and vaccine development.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- USP18 modulates lupus risk via negative regulation of interferon response 96%
- COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types. 96%
- Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis. 96%
Similar papers in this journal
- Mapping pQTLs of circulating inflammatory proteins identifies drivers of immune-related disease risk and novel therapeutic targets 96%
- Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program 96%
- Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis 96%
Similar papers in this journal
- Gene regulatory network inference from CRISPR perturbations in primary CD4+ T cells elucidates the genomic basis of immune disease 97%
- Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe 96%
- Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts 96%
Similar papers in this journal
- Integrating Natural and Engineered Genetic Variation to Decode Regulatory Influence on Blood Traits 96%
- Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors 95%
- The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state and its deletion improves checkpoint blockade 94%
Similar papers in this journal
- Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements 97%
- Chromatin accessibility variation provides insights into missing regulation underlying immune-mediated diseases 97%
- RAG suppresses group 2 innate lymphoid cells 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.