Evidence map›Paper›PMID 41999581›Full record

ArticleThe Journal of infectious diseases2026

Human Genetic Variation Associates With Infection by Derived Ugandan M. tuberculosis Lineage.

Catherine M Stein, Penelope Benchek, Lentlamatse Mantshoyane, Timothy Ciesielski, Michael L McHenry, Himiede Wilson-Sesay, Moses Joloba, Eddie Wampande, Kimberly A Dill Mc-Farland, Allison W Roberts and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Catherine M SteinDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000-0002-9763-5023
Penelope BenchekDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Lentlamatse MantshoyaneDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000-0002-5785-6809
Timothy CiesielskiDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Michael L McHenryDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
Himiede Wilson-SesayDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000-0001-8400-6511
Moses JolobaSchool for Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
Eddie WampandeSchool for Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
Kimberly A Dill Mc-FarlandDepartment of Allergy and Infectious Diseases, School of Medicine, University of Washington, Seattle, Washington, USA.
Allison W RobertsDepartment of Molecular and Cell Biology, University of California, Berkeley, California, USA.
Ben PolaccoQuantitative Biosciences Institute and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.
Max BennettQuantitative Biosciences Institute and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.ORCID 0009-0004-1318-3026
Nevan KroganQuantitative Biosciences Institute and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.ORCID 0000-0003-4902-337X
W Henry BoomDivision of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Jeffery S CoxDepartment of Molecular and Cell Biology, University of California, Berkeley, California, USA.
Harriet Mayanja-KizzaDepartment of Medicine, School of Medicine, Makerere University and Mulago Hospital, Kampala, Uganda.
Thomas R HawnDepartment of Allergy and Infectious Diseases, School of Medicine, University of Washington, Seattle, Washington, USA.
Scott M WilliamsDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000-0002-4835-9544

Funding

Systems Biology, Bioinformatics, & Data IntegrationU19AI162583 · NIAID · UNIVERSITY OF WASHINGTON · PI COX, JEFFERY S, HAWN, THOMAS R · 2021 to 2025
$13.0M
Resistance to MTB infection in HIV infected individuals in Uganda and S. AfricaR01AI124348 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BOOM, W. HENRY, HAWN, THOMAS R · 2016 to 2020
$11.3M
BIOMETRIC-GENETIC ANALYSIS OF CARDIOVASCULAR DISEASET32HL007567 · NHLBI · LOUISIANA STATE UNIV HSC NEW ORLEANS · PI ZHU, XIAOFENG · 1985 to 2021
$6.0M
Tuberculosis Prevention Research Unit /TBRU/-266095383N01AI095383 · NIAID · CASE WESTERN RESERVE UNIVERSITY · 2000 to 2005
$5.6M
Pathway analysis of tuberculosis pathogenesisR01HL096811 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI STEIN, CATHERINE MARIE · 2009 to 2013
$2.2M
TUBERCULOSIS PREVENTION RESEARCH UNITN01AI95383 · NIAID · PI BOOM, W. HENRY · 2007 to 2007
$1.5M
NHLBI NIH HHS R01 HL096811NHLBI NIH HHS T32 HL007567NIAID NIH HHS N01 AI095383NIAID NIH HHS R01 AI124348NIAID NIH HHS U19 AI162583NIH HHS N01 AI95383NIH HHS R01AI124348NIH HHS R01HL096811NIH HHS T32HL007567NIH HHS U19AI162583
6 · The paper itself

Abstract

backgroundSeveral studies have examined host and pathogen genetic influences on tuberculosis (TB) susceptibility separately, but relatively few studied their combined effects. However, host-pathogen interactions or co-evolution may explain the inability to replicate many reported human genetic effects across global populations and provide additional insight into TB risk. In this study, we address such possible interactions by focusing on the outcome of infection with the L4-Uganda M. tuberculosis sub-lineage and human genetic variants as independent variables. This is possible because the L4-Uganda sub-lineage is both restricted to Uganda and nearby locations and is recent there, compared with other more ancestral L4 lineages.

methodsOur study consisted of 276 culture-confirmed adult TB cases from a long-standing household contact study. We conducted a genome-wide association study, with infection with L4-Uganda versus L4-NonUganda as the outcome.

resultsMultiple loci with results suggestive of association (P < 10-5) also demonstrated convergent relevant evidence for strain specific infection via: evidence of gene expression in relevant cells and lung tissue, signatures of natural selection, eQTL expression, and CRISPR screens for immunity-related genes. We also replicated previously published host-pathogen interaction effects, demonstrating that effects seen for other sub-lineages were also present for L4-Uganda.

conclusionsThese results provide evidence for host-pathogen co-evolution in TB, consistent with our previous work, and indicate these interactions involve genes highly relevant to the host immune response to Mycobacterium infection.

Indexed as

Genetic Predisposition to DiseaseGenetic VariationHost-Pathogen InteractionsMycobacterium tuberculosisTuberculosisAdultFemaleGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideUgandaco-evolutionGWAShost-pathogen interactionimmunogeneticstuberculosis susceptibility

Identifiers

PMID41999581
PMCPMC13600372

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.