Tuberculin skin test negativity is under tight genetic control of chromosomal region 11p14-15 in settings with different tuberculosis endemicities.
Bottom Line: A genome-wide analysis of TST negativity identified a significant linkage signal (P < 3 × 10(-5)) in close vicinity of TST1.Combined analysis of the 2 samples increased evidence of linkage (P = 2.4 × 10(-6)), further implicating genetic factors located on 11p14-15.This region overlaps the TNF1 locus controlling mycobacteria-driven tumor necrosis factor α production.
Affiliation: McGill International TB Centre Department of Human Genetics Department of Medicine, McGill University, Montreal, Canada.Show MeSH
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Mentions: Second, from the French sample, 97 nuclear families, including 237 offspring, were informative for linkage analysis (ie, composed of at least 2 genotyped sibs with a TST value). Characteristics of the 237 offspring are shown in Supplementary Table 1. Among them, only 4 had not received BCG vaccine, eliminating BCG vaccination as a potential confounding factor in our study. Results of the GWLA of TST-bin adjusted on the covariates are presented in Figure 1A. Information content was high across all autosomes, with mean genome-wide information of approximately 90%. We identified 1 major locus, at position 14.3 Mb on chromosomal region 11p15, that reached the threshold commonly used to claim genome-wide significance (LOD score, 3.65; P = 2.08 × 10−5; Figure 1A). In addition, we identified 18 weaker linkage peaks with a P value of <.01 (Supplementary Table 2).Figure 1.
Affiliation: McGill International TB Centre Department of Human Genetics Department of Medicine, McGill University, Montreal, Canada.