Novel Genetic Locus Associated with Resistance toInfection: A Multi-Ancestry Genome-Wide Association Study.
Neel R Gandhi, Matheus Fernandes Gyorfy, Mandar Paradkar, Nombuyiselo Jennet Mofokeng, Marina C Figueiredo, Senbagavalli Prakash, Kamakshi Prudhula Devalraju, Qin Hui, et al. (30 authors)
medRxiv : the preprint server for health sciences · 2026-03
Abstract
Understanding host susceptibility to(is critical for the development of new vaccines. Certain individuals "resist" becoming infected withdespite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" toinfection across populations. Here we conducted a genome-wide association study (GWAS) of resistance toinfection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free ofinfection 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-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 toinfection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection frominfection.