Novel Genetic Locus Associated with Resistance to M. tuberculosis Infection: A Multi-Ancestry Genome-Wide Association Study
Gandhi, N. R.; Fernandes Gyorfy, M.; Paradkar, M.; Jennet Mofokeng, N.; Figueiredo, M. C.; Prakash, S.; Prudhula Devalraju, K.; Hui, Q.; Willis, F.; Mave, V.; Andrade, B. B.; Moloantoa, T.; Kumar Neela, V. S.; Campbell, A.; Liu, C.; Young, A.; Cordeiro-Santos, M.; Gaikwad, S.; Karyakarte, R. P.; Rolla, V. C.; Kritski, A. L.; Collins, J. M.; Shah, N. S.; Brust, J. C. M.; Lakshmi Valluri, V.; Sarkar, S.; Sterling, T. R.; Martinson, N. A.; Gupta, A.; Sun, Y. V.
Show abstract
Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb 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 Mtb 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 Mtb-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 Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.
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