TY - GEN AB - 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 <i>Mycobacterium tuberculosis</i> 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, <i>P</i> = 7.92 × 10<sup>−8</sup>) in the <i>FLOT1</i> gene and a subclavaluee of <i>Mtb</i> 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. AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Harvard University AD - Harvard University AD - Harvard University AD - University of Chicago AD - Harvard University AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Advanced Research and Health AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AD - Harvard University AD - Harvard University AD - Brigham and Women’s Hospital AD - Brigham and Women’s Hospital AU - Luo, Yang AU - Huang, Chuan-Chin AU - Howard, Nicole C. AU - Wang, Xin AU - Liu, Qingyun AU - Li, Xinyi AU - Zhu, Junhao AU - Amariuta, Tiffany AU - Asgari, Samira AU - Ishigaki, Kazuyoshi AU - Calderon, Roger AU - Raman, Sahadevan AU - Ramnarine, Alexandrea K. AU - Mayfield, Jacob A. AU - Moody, D. Branch AU - Lecca, Leonid AU - Fortune, Sarah M. AU - Murray, Megan B. AU - Raychaudhuri, Soumya DA - 2024-11-29 ID - 14179 JF - Nature Communications L1 - https://knowledge.uchicago.edu/record/14179/files/Paired-analysis-of-host-and-pathogen-genomes-identifies-determinants-of-human-tuberculosis.pdf L1 - https://knowledge.uchicago.edu/record/14179/files/Source-data.zip L1 - https://knowledge.uchicago.edu/record/14179/files/Supplementary-information.zip L1 - https://knowledge.uchicago.edu/record/14179/files/41467_2024_54741_MOESM3_ESM.xlsx L2 - https://knowledge.uchicago.edu/record/14179/files/Paired-analysis-of-host-and-pathogen-genomes-identifies-determinants-of-human-tuberculosis.pdf L2 - https://knowledge.uchicago.edu/record/14179/files/Source-data.zip L2 - https://knowledge.uchicago.edu/record/14179/files/Supplementary-information.zip L2 - https://knowledge.uchicago.edu/record/14179/files/41467_2024_54741_MOESM3_ESM.xlsx L4 - https://knowledge.uchicago.edu/record/14179/files/Paired-analysis-of-host-and-pathogen-genomes-identifies-determinants-of-human-tuberculosis.pdf L4 - https://knowledge.uchicago.edu/record/14179/files/Source-data.zip L4 - https://knowledge.uchicago.edu/record/14179/files/Supplementary-information.zip L4 - https://knowledge.uchicago.edu/record/14179/files/41467_2024_54741_MOESM3_ESM.xlsx LA - eng LK - https://knowledge.uchicago.edu/record/14179/files/Paired-analysis-of-host-and-pathogen-genomes-identifies-determinants-of-human-tuberculosis.pdf LK - https://knowledge.uchicago.edu/record/14179/files/Source-data.zip LK - https://knowledge.uchicago.edu/record/14179/files/Supplementary-information.zip LK - https://knowledge.uchicago.edu/record/14179/files/41467_2024_54741_MOESM3_ESM.xlsx N2 - 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 <i>Mycobacterium tuberculosis</i> 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, <i>P</i> = 7.92 × 10<sup>−8</sup>) in the <i>FLOT1</i> gene and a subclavaluee of <i>Mtb</i> 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. PY - 2024-11-29 T1 - Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis TI - Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis UR - https://knowledge.uchicago.edu/record/14179/files/Paired-analysis-of-host-and-pathogen-genomes-identifies-determinants-of-human-tuberculosis.pdf UR - https://knowledge.uchicago.edu/record/14179/files/Source-data.zip UR - https://knowledge.uchicago.edu/record/14179/files/Supplementary-information.zip UR - https://knowledge.uchicago.edu/record/14179/files/41467_2024_54741_MOESM3_ESM.xlsx Y1 - 2024-11-29 ER -