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  -