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Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis

Author

Listed:
  • Yang Luo

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Chuan-Chin Huang

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Nicole C. Howard

    (Harvard T. H. Chan School of Public Health)

  • Xin Wang

    (Harvard T. H. Chan School of Public Health)

  • Qingyun Liu

    (Harvard T. H. Chan School of Public Health
    University of North Carolina at Chapel Hill)

  • Xinyi Li

    (University of Chicago)

  • Junhao Zhu

    (Harvard T. H. Chan School of Public Health)

  • Tiffany Amariuta

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Samira Asgari

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Kazuyoshi Ishigaki

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Roger Calderon

    (Advanced Research and Health)

  • Sahadevan Raman

    (Harvard Medical School)

  • Alexandrea K. Ramnarine

    (Harvard Medical School)

  • Jacob A. Mayfield

    (Harvard Medical School)

  • D. Branch Moody

    (Harvard Medical School)

  • Leonid Lecca

    (Harvard Medical School
    Socios En Salud Sucursal Peru)

  • Sarah M. Fortune

    (Harvard T. H. Chan School of Public Health
    MIT and Harvard)

  • Megan B. Murray

    (Brigham and Women’s Hospital
    Harvard Medical School
    Harvard T.H Chan School of Public Health)

  • Soumya Raychaudhuri

    (Harvard Medical School
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

Abstract

Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 − 20.77, P = 7.92 × 10−8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Suggested Citation

  • Yang Luo & Chuan-Chin Huang & Nicole C. Howard & Xin Wang & Qingyun Liu & Xinyi Li & Junhao Zhu & Tiffany Amariuta & Samira Asgari & Kazuyoshi Ishigaki & Roger Calderon & Sahadevan Raman & Alexandrea , 2024. "Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54741-w
    DOI: 10.1038/s41467-024-54741-w
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    References listed on IDEAS

    as
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