Novel Genetic Locus Associated with Resistance to <i>M. tuberculosis</i> Infection: A Multi-Ancestry Genome-Wide Association Study
Understanding host susceptibility to <i>Mycobacterium tuberculosis</i> ( <i>Mtb)</i> is critical for the development of new vaccines. Certain individuals "resist" becoming infected with <i>Mtb</i> despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to <i>Mtb</i> infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to <i>Mtb</i> infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of <i>Mtb</i> infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing <i>Mtb</i> -infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to <i>Mtb</i> infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from <i>Mtb</i> infection.
Authors
- Satya Prakash (ORCID: https://orcid.org/0000-0001-6814-8106)
- Tumelo Moloantoa
- Marcelo Cordeiro-dos-Santos
- Alexandra Young (ORCID: https://orcid.org/0000-0003-4807-7675)
- Kamakshi Prudhula Devalraju (ORCID: https://orcid.org/0000-0003-2755-7469)
- Marina C. Figueiredo (ORCID: https://orcid.org/0000-0002-0671-398X)
- Fay Willis
- S. Sarkar
- Venkata Sanjeev Kumar Neela (ORCID: https://orcid.org/0000-0003-3847-0182)
- Matheus Fernandes Gyorfy (ORCID: https://orcid.org/0000-0002-2027-8128)
- Vijaya Lakshmi Valluri (ORCID: https://orcid.org/0000-0002-0462-4174)
- Mave
- Neil Alexander Martinson (ORCID: https://orcid.org/0000-0002-0184-5705)
- Mandar Paradkar (ORCID: https://orcid.org/0000-0001-9843-4656)
- James C.M. Brust
- B. C. O. P. Andrade (ORCID: https://orcid.org/0000-0003-2321-7811)
- Sanjay N Gaikwad
- Amita Gupta
- Qin Hui
- Neel R. Gandhi
- Angela Campbell
- Chang Liu
- Nombuyiselo Jennet Mofokeng
- N. Sarita Shah
- Jeffrey M. Collins
- Yan V. Sun
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Albert Einstein College of Medicine (US)
- Johns Hopkins University (US)
- Emory University (US)
- University of the Witwatersrand (ZA)
- B. J. Medical College & Sassoon Hospital (IN)
- Johns Hopkins Medicine (US)
- Fundação de Medicina Tropical (BR)
- Universidade Nilton Lins (BR)
- Universidade do Estado do Amazonas (BR)
- Perinatal HIV Research Unit (ZA)
- Government Medical College (IN)
- Fundação Oswaldo Cruz (BR)
- Jawaharlal Institute of Post Graduate Medical Education and Research (IN)
- Universidade Federal do Estado do Rio de Janeiro (BR)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-03-07
- DOI
- https://doi.org/10.64898/2026.03.06.26347614
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- CRDF Global
- City University of New York
- Emory University
- National Institutes of Health
- Center for AIDS Research, University of Washington
- Medical Research Council
- National Institute of Allergy and Infectious Diseases