ArticleGenome medicine2025
A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.
Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
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32 authors.
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Abstract
backgroundDespite sustained exposure to Mycobacterium tuberculosis (Mtb), some individuals-so-called resisters-have persistently negative results for the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). "Resistance to immune conversion" is the best-known clinical correlate for absence of Mtb transmission and protection from tuberculosis (TB). We investigated the human genetic basis of this phenotype by hypothesizing that resisters living with HIV, a major risk factor for TB, would be enriched in genotypes conferring resistance.
methodsWe enrolled two cohorts of people living with HIV (PWH), consisting of 55 resisters and 100 controls-either positive for TST and IGRA or with a history of TB-from South Africa, and 66 resisters and 57 controls from Haiti, two regions where TB is hyperendemic. All study participants underwent whole-genome sequencing (WGS). We performed a genome-wide association study (GWAS) of the resister phenotype, focusing on a comprehensive set of 320,629 common protein-altering and regulatory variants.
resultsWe identified a cluster of variants on chromosome 12q15, including rs622656, associated with the resister phenotype in both South Africa and Haiti. A meta-analysis revealed that the C allele of rs622656 was associated with the resister phenotype with an odds ratio (OR) of 4.35 (95% CI: 2.44-7.69) (P = 2.47 × 10
conclusionsWe report a new cluster of variants on chromosome 12q15, overlapping the YEATS4 gene, strongly associated with the resister phenotype in two populations of PWH. Our results contribute to the understanding of the molecular mechanisms that block transmission of Mtb.
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