TY - JOUR
T1 - Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis
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
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
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 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.
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 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.
UR - https://www.scopus.com/pages/publications/85211181384
U2 - 10.1038/s41467-024-54741-w
DO - 10.1038/s41467-024-54741-w
M3 - Article
C2 - 39613754
AN - SCOPUS:85211181384
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10393
ER -