ArticlePLoS genetics2020
Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pooled it
- Human Genetic Variation Associates With Infection by Derived Ugandan M. tuberculosis Lineage.The Journal of infectious diseases · 2026Article
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Association of the FTO gene polymorphism with the features of the clinical course of tuberculosis infection.BMC infectious diseases · 2026Article
- Human genetic ancestry,eLife · 2026Article
- Alveolar macrophage transcriptional signatures associated with resistance to TST/IGRA conversion following Mycobacterium tuberculosis exposure.BMC genomics · 2025Article
- ESX-5 Deletions inbioRxiv : the preprint server for biology · 2025Article
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania.BMC medical genomics · 2025Article
- Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials.Frontiers in antibiotics · 2025Review
- Genomic variations in Mycobacterium tuberculosis from the lungs and blood of HIV-infected individuals in Uganda: insights into compartmentalization.African health sciences · 2024Article
- Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis.Nature communications · 2024Article
- Comparative Genomic Analysis ofTropical medicine and infectious disease · 2024Article
- Factors Associated with Extended Hospital Stay and its Impact on Subsequent Short-term Readmission with Tuberculosis Patients.Archives of Iranian medicine · 2024Observational
- Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania.Scientific reports · 2024Article
- Evolution and emergence of Mycobacterium tuberculosis.FEMS microbiology reviews · 2024Review
- Understanding the development of tuberculous granulomas: insights into host protection and pathogenesis, a review in humans and animals.Frontiers in immunology · 2024Review
- Tuberculosis Severity Predictive Model Using Mtb Variants and Serum Biomarkers in a Colombian Cohort of APTB Patients.Biomedicines · 2023Article
- Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.The clinical respiratory journal · 2023Article
- High Lethality ofInfection and immunity · 2023Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 5 countries.
Funding
Abstract
Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which there were 3 MTB lineages of which L4-Ugandan (L4.6) is the most recent. TB severity, measured using the Bandim TBscore, was modeled as a function of host SNP genotype, MTB lineage, and their interaction, within two independent cohorts of TB cases, N = 113 and 121. No association was found between lineage and severity, but association between multiple polymorphisms in IL12B and TBscore was replicated in two independent cohorts (most significant rs3212227, combined p = 0.0006), supporting previous associations of IL12B with TB susceptibility. We also observed significant interaction between a single nucleotide polymorphism (SNP) in SLC11A1 and the L4-Ugandan lineage in both cohorts (rs17235409, meta p = 0.0002). Interestingly, the presence of the L4-Uganda lineage in the presence of the ancestral human allele associated with more severe disease. These findings demonstrate that IL12B is associated with severity of TB in addition to susceptibility, and that the association between TB severity and human genetics can be due to an interaction between genes in the two species, consistent with host-pathogen coevolution in TB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.