ArticlePLoS genetics2023
Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation.
Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Post-Tuberculosis Lung Disease: Clinicopathologic Insights, Diagnosis, Prevention, and Management.MedComm · 2026Review
- Human Genetic Variation Associates With Infection by Derived Ugandan M. tuberculosis Lineage.The Journal of infectious diseases · 2026Article
- Beyond the Lungs: Cardiovascular Risk in COPD Patients with a History of Tuberculosis-A Narrative Review.Journal of clinical medicine · 2026Review
- Integrative multi-omics analysis reveals cellular and molecular insights into gestational diabetes mellitus.Frontiers in molecular biosciences · 2026Article
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- A Genome-Wide Association Study of Taste Liking in the Danish Population.The Journal of nutrition · 2025Article
- Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses.The Journal of clinical investigation · 2025Article
- ULK1 gene polymorphisms and severe tuberculosis in the Chinese Han population: a case-control study.Frontiers in medicine · 2025Article
- Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis.Nature communications · 2024Article
- CD4International journal of molecular sciences · 2024Article
- Article
- Genetic epidemiology of resistance to M. tuberculosis Infection: importance of study design and recent findings.Genes and immunity · 2023Review
- Serum pro-inflammatory biomarkers associated with improvement in quality of life in pulmonary tuberculosis.Frontiers in immunology · 2023Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundTuberculosis (TB) remains a major public health problem globally, even compared to COVID-19. Genome-wide studies have failed to discover genes that explain a large proportion of genetic risk for adult pulmonary TB, and even fewer have examined genetic factors underlying TB severity, an intermediate trait impacting disease experience, quality of life, and risk of mortality. No prior severity analyses used a genome-wide approach. METHODS AND
findingsAs part of our ongoing household contact study in Kampala, Uganda, we conducted a genome-wide association study (GWAS) of TB severity measured by TBScore, in two independent cohorts of culture-confirmed adult TB cases (n = 149 and n = 179). We identified 3 SNPs (P<1.0 x 10-7) including one on chromosome 5, rs1848553, that was GWAS significant (meta-analysis p = 2.97x10-8). All three SNPs are in introns of RGS7BP and have effect sizes corresponding to clinically meaningful reductions in disease severity. RGS7BP is highly expressed in blood vessels and plays a role in infectious disease pathogenesis. Other genes with suggestive associations defined gene sets involved in platelet homeostasis and transport of organic anions. To explore functional implications of the TB severity-associated variants, we conducted eQTL analyses using expression data from Mtb-stimulated monocyte-derived macrophages. A single variant (rs2976562) associated with monocyte SLA expression (p = 0.03) and subsequent analyses indicated that SLA downregulation following MTB stimulation associated with increased TB severity. Src Like Adaptor (SLAP-1), encoded by SLA, is highly expressed in immune cells and negatively regulates T cell receptor signaling, providing a potential mechanistic link to TB severity.
conclusionsThese analyses reveal new insights into the genetics of TB severity with regulation of platelet homeostasis and vascular biology being central to consequences for active TB patients. This analysis also reveals genes that regulate inflammation can lead to differences in severity. Our findings provide an important step in improving TB patient outcomes.
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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.