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We conduct a genome-to-genome study of paired human and\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR\u2009=\u200910.06, 95%CI: 4.87 \u2212 20.77,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20097.92\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) in the\n                    <jats:italic>FLOT1<\/jats:italic>\n                    gene and a subclavaluee of\n                    <jats:italic>Mtb<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-54741-w","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T09:14:30Z","timestamp":1732871670000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-6166","authenticated-orcid":false,"given":"Yang","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Chin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6930-3347","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-5050","authenticated-orcid":false,"given":"Qingyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3301-5677","authenticated-orcid":false,"given":"Junhao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Amariuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Asgari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Ishigaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-0489","authenticated-orcid":false,"given":"Roger","family":"Calderon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-8169","authenticated-orcid":false,"given":"Sahadevan","family":"Raman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-8648","authenticated-orcid":false,"given":"Alexandrea K.","family":"Ramnarine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-6755","authenticated-orcid":false,"given":"Jacob A.","family":"Mayfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-3058","authenticated-orcid":false,"given":"D. 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