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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

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    1. Francesc Coll & Ruth McNerney & José Afonso Guerra-Assunção & Judith R. Glynn & João Perdigão & Miguel Viveiros & Isabel Portugal & Arnab Pain & Nigel Martin & Taane G. Clark, 2014. "A robust SNP barcode for typing Mycobacterium tuberculosis complex strains," Nature Communications, Nature, vol. 5(1), pages 1-5, December.
    2. Jeffery S. Cox & Bing Chen & Michael McNeil & William R. Jacobs, 1999. "Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice," Nature, Nature, vol. 402(6757), pages 79-83, November.
    3. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    4. Kirsten I. Bos & Kelly M. Harkins & Alexander Herbig & Mireia Coscolla & Nico Weber & Iñaki Comas & Stephen A. Forrest & Josephine M. Bryant & Simon R. Harris & Verena J. Schuenemann & Tessa J. Campbe, 2014. "Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis," Nature, Nature, vol. 514(7523), pages 494-497, October.
    5. Maha R. Farhat & Luca Freschi & Roger Calderon & Thomas Ioerger & Matthew Snyder & Conor J. Meehan & Bouke de Jong & Leen Rigouts & Alex Sloutsky & Devinder Kaur & Shamil Sunyaev & Dick van Soolingen , 2019. "GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    6. Yang Luo & Sara Suliman & Samira Asgari & Tiffany Amariuta & Yuriy Baglaenko & Marta Martínez-Bonet & Kazuyoshi Ishigaki & Maria Gutierrez-Arcelus & Roger Calderon & Leonid Lecca & Segundo R. León & J, 2019. "Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    7. Katrin D. Mayer-Barber & Bruno B. Andrade & Sandra D. Oland & Eduardo P. Amaral & Daniel L. Barber & Jacqueline Gonzales & Steven C. Derrick & Ruiru Shi & Nathella Pavan Kumar & Wang Wei & Xing Yuan &, 2014. "Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk," Nature, Nature, vol. 511(7507), pages 99-103, July.
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