ArticleAmerican journal of human genetics2016
A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Genetic Determinants of Infectious Diseases in the Qatari Population.Epidemiologia (Basel, Switzerland) · 2026Article
- Analysis of risk factors for latent tuberculosis infection among type 2 diabetics: a hospital-based multicenter cross-sectional study.Frontiers in cellular and infection microbiology · 2026Article
- Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania.BMC medical genomics · 2025Article
- Insights into protection against Mycobacterium tuberculosis infection: time to officially confirm another phenotype?The Journal of clinical investigation · 2025Article
- miR-4687-5p Affects Intracellular Survival ofMicroorganisms · 2024Article
- Genetic epidemiology of resistance to M. tuberculosis Infection: importance of study design and recent findings.Genes and immunity · 2023Review
- Fulminant pulmonary tuberculosis in a previously healthy young woman from the Marshall Islands: Potential risk factors.Journal of clinical tuberculosis and other mycobacterial diseases · 2023Review
- Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study.medRxiv : the preprint server for health sciences · 2023Article
- Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.Nature communications · 2022Article
- REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection.Nature microbiology · 2022Article
- Offense and Defense in Granulomatous Inflammation Disease.Frontiers in cellular and infection microbiology · 2022Review
- BCG-induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next-generation vaccines.Immunological reviews · 2021Review
- These Are the Genes You're Looking For: Finding Host Resistance Genes.Trends in microbiology · 2021Review
- Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci inFrontiers in genetics · 2021Article
- Local Ancestry Adjusted Allelic Association Analysis Robustly Captures Tuberculosis Susceptibility Loci.Frontiers in genetics · 2021Article
- Genetics and evolution of tuberculosis pathogenesis: New perspectives and approaches.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Review
- Article
- Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?PLoS genetics · 2020Article
- Article
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Authors and funding
25 authors at 12 institutions in 7 countries.
Funding
Abstract
Immunosuppression resulting from HIV infection increases the risk of progression to active tuberculosis (TB) both in individuals newly exposed to Mycobacterium tuberculosis (MTB) and in those with latent infections. We hypothesized that HIV-positive individuals who do not develop TB, despite living in areas where it is hyperendemic, provide a model of natural resistance. We performed a genome-wide association study of TB resistance by using 581 HIV-positive Ugandans and Tanzanians enrolled in prospective cohort studies of TB; 267 of these individuals developed active TB, and 314 did not. A common variant, rs4921437 at 5q33.3, was significantly associated with TB (odds ratio = 0.37, p = 2.11 × 10(-8)). This variant lies within a genomic region that includes IL12B and is embedded in an H3K27Ac histone mark. The locus also displays consistent patterns of linkage disequilibrium across African populations and has signals of strong selection in populations from equatorial Africa. Along with prior studies demonstrating that therapy with IL-12 (the cytokine encoded in part by IL12B, associated with longer survival following MTB infection in mice deficient in CD4 T cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating TB, especially for HIV-positive individuals. Our results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease.
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