{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:21:05Z","timestamp":1768566065725,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,29]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":95,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The heterogeneity of outcomes after\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb) exposure is a conundrum associated with millennia of host-pathogen co-evolution. We hypothesized that human myeloid cells contain genetically encoded, Mtb-specific responses that regulate critical steps in tuberculosis (TB) pathogenesis. We mapped genome-wide expression quantitative trait loci (eQTLs) in Mtb-infected monocytes with RNAseq from 80 Ugandan household contacts of pulmonary TB cases to identify monocyte-specific, Mtb-dependent eQTLs and their association with cytokine expression and clinical resistance to tuberculin skin test (TST) and interferon-\u03b3 release assay (IGRA) conversion. cis-eQTLs (n=1,567) were identified in Mtb-infected monocytes (FDR&lt;0.01), including 29 eQTLs in 16 genes which were Mtb-dependent (significant for Mtb:genotype interaction [FDR&lt;0.1], but not classified as eQTL in media condition [FDR\u22650.01]). A subset of eQTLs were associated with Mtb-induced cytokine expression (n=8) and\/or clinical resistance to TST\/IGRA conversion (n=1). Expression of\n                  <jats:italic>BMP6<\/jats:italic>\n                  , an Mtb-dependent eQTL gene, was associated with\n                  <jats:italic>IFNB1<\/jats:italic>\n                  induction in Mtb-infected and DNA ligand-induced cells. Network and enrichment analyses identified fatty acid metabolism as a pathway associated with eQTL genes. These findings suggest that monocyte genes contain Mtb-dependent eQTLs, including a subset associated with cytokine expression and\/or clinical resistance to TST\/IGRA conversion, providing insight into immunogenetic pathways regulating susceptibility to Mtb infection and TB pathogenesis.\n                <\/jats:p>","DOI":"10.1101\/2023.08.28.23294698","type":"posted-content","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T02:20:13Z","timestamp":1693362013000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Mycobacterium tuberculosis<\/i>\n                  -dependent Monocyte Expression Quantitative Trait Loci and Tuberculosis Pathogenesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3141-7506","authenticated-orcid":false,"given":"Hyejeong","family":"Hong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-7065","authenticated-orcid":false,"given":"Kimberly A.","family":"Dill-McFarland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason D.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenna J.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope","family":"Benchek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harriet","family":"Mayanja-Kizza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Henry","family":"Boom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine M.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Hawn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023090112150442000_2023.08.28.23294698v1.1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ijid.2022.05.029","article-title":"Prevalence trends of latent tuberculosis infection at the global, regional, and country levels from 1990-2019","volume":"122","year":"2022","journal-title":"Int J Infect Dis"},{"key":"2023090112150442000_2023.08.28.23294698v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00545.x"},{"key":"2023090112150442000_2023.08.28.23294698v1.3","first-page":"828939","article-title":"Risk factors for tuberculosis","volume":"2013","year":"2013","journal-title":"Pulmonary medicine"},{"issue":"1","key":"2023090112150442000_2023.08.28.23294698v1.4","first-page":"E9","article-title":"The history of tuberculosis: from the first historical records to the isolation of Koch\u2019s bacillus","volume":"58","year":"2017","journal-title":"Journal of preventive medicine and hygiene"},{"key":"2023090112150442000_2023.08.28.23294698v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2020.104204"},{"key":"2023090112150442000_2023.08.28.23294698v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng.639"},{"key":"2023090112150442000_2023.08.28.23294698v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1080"},{"key":"2023090112150442000_2023.08.28.23294698v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3248"},{"key":"2023090112150442000_2023.08.28.23294698v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3498"},{"issue":"1","key":"2023090112150442000_2023.08.28.23294698v1.10","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1038\/s41467-019-11664-1","article-title":"Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians","volume":"10","year":"2019","journal-title":"Nature Communications"},{"key":"2023090112150442000_2023.08.28.23294698v1.11","doi-asserted-by":"crossref","first-page":"103727","DOI":"10.1016\/j.ebiom.2021.103727","article-title":"Resistance to TST\/IGRA conversion in Uganda: Heritability and Genome-Wide Association Study","volume":"74","year":"2021","journal-title":"EBioMedicine"},{"key":"2023090112150442000_2023.08.28.23294698v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s12561-012-9068-3"},{"key":"2023090112150442000_2023.08.28.23294698v1.13","doi-asserted-by":"crossref","unstructured":"Simmons, J.D. , et al., Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test\/interferon-\u03b3 release assay conversion. 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