Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations. Quistrebert, J., Orlova, M., Kerner, G., Ton, L. T., Luong, N. T., Danh, N. T., Vincent, Q. B., Jabot-Hanin, F., Seeleuthner, Y., Bustamante, J., Boisson-Dupuis, S., Huong, N. T., Ba, N. N., Casanova, J., Delacourt, C., Hoal, E. G., Alcaïs, A., Thai, V. H., Thành, L. T., Abel, L., Schurr, E., & Cobat, A. PLoS genetics, 17(3):e1009392, March, 2021. doi abstract bibtex The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.
@article{quistrebert_genome-wide_2021,
title = {Genome-wide association study of resistance to {Mycobacterium} tuberculosis infection identifies a locus at 10q26.2 in three distinct populations},
volume = {17},
issn = {1553-7404},
doi = {10.1371/journal.pgen.1009392},
abstract = {The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95\%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95\%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.},
language = {eng},
number = {3},
journal = {PLoS genetics},
author = {Quistrebert, Jocelyn and Orlova, Marianna and Kerner, Gaspard and Ton, Le Thi and Luong, Nguyễn Trong and Danh, Nguyễn Thanh and Vincent, Quentin B. and Jabot-Hanin, Fabienne and Seeleuthner, Yoann and Bustamante, Jacinta and Boisson-Dupuis, Stéphanie and Huong, Nguyen Thu and Ba, Nguyen Ngoc and Casanova, Jean-Laurent and Delacourt, Christophe and Hoal, Eileen G. and Alcaïs, Alexandre and Thai, Vu Hong and Thành, Lai The and Abel, Laurent and Schurr, Erwin and Cobat, Aurélie},
month = mar,
year = {2021},
pmid = {33661925},
pages = {e1009392},
}
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T.","Abel, L.","Schurr, E.","Cobat, A."],"bibdata":{"bibtype":"article","type":"article","title":"Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations","volume":"17","issn":"1553-7404","doi":"10.1371/journal.pgen.1009392","abstract":"The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). The locus was replicated in a French multi-ethnic HHC cohort and a familial admixed cohort from a hyper-endemic area of South Africa, with an overall OR for rs17155120 estimated at 0.50 (95%CI 0.45-0.55, P = 1.26×10-9). The variants are located in intronic regions and upstream of C10orf90, a tumor suppressor gene which encodes an ubiquitin ligase activating the transcription factor p53. In silico analysis showed that the protective alleles were associated with a decreased expression in monocytes of the nearby gene ADAM12 which could lead to an enhanced response of Th17 lymphocytes. Our results reveal a novel locus controlling resistance to M. tuberculosis infection across different populations.","language":"eng","number":"3","journal":"PLoS genetics","author":[{"propositions":[],"lastnames":["Quistrebert"],"firstnames":["Jocelyn"],"suffixes":[]},{"propositions":[],"lastnames":["Orlova"],"firstnames":["Marianna"],"suffixes":[]},{"propositions":[],"lastnames":["Kerner"],"firstnames":["Gaspard"],"suffixes":[]},{"propositions":[],"lastnames":["Ton"],"firstnames":["Le","Thi"],"suffixes":[]},{"propositions":[],"lastnames":["Luong"],"firstnames":["Nguyễn","Trong"],"suffixes":[]},{"propositions":[],"lastnames":["Danh"],"firstnames":["Nguyễn","Thanh"],"suffixes":[]},{"propositions":[],"lastnames":["Vincent"],"firstnames":["Quentin","B."],"suffixes":[]},{"propositions":[],"lastnames":["Jabot-Hanin"],"firstnames":["Fabienne"],"suffixes":[]},{"propositions":[],"lastnames":["Seeleuthner"],"firstnames":["Yoann"],"suffixes":[]},{"propositions":[],"lastnames":["Bustamante"],"firstnames":["Jacinta"],"suffixes":[]},{"propositions":[],"lastnames":["Boisson-Dupuis"],"firstnames":["Stéphanie"],"suffixes":[]},{"propositions":[],"lastnames":["Huong"],"firstnames":["Nguyen","Thu"],"suffixes":[]},{"propositions":[],"lastnames":["Ba"],"firstnames":["Nguyen","Ngoc"],"suffixes":[]},{"propositions":[],"lastnames":["Casanova"],"firstnames":["Jean-Laurent"],"suffixes":[]},{"propositions":[],"lastnames":["Delacourt"],"firstnames":["Christophe"],"suffixes":[]},{"propositions":[],"lastnames":["Hoal"],"firstnames":["Eileen","G."],"suffixes":[]},{"propositions":[],"lastnames":["Alcaïs"],"firstnames":["Alexandre"],"suffixes":[]},{"propositions":[],"lastnames":["Thai"],"firstnames":["Vu","Hong"],"suffixes":[]},{"propositions":[],"lastnames":["Thành"],"firstnames":["Lai","The"],"suffixes":[]},{"propositions":[],"lastnames":["Abel"],"firstnames":["Laurent"],"suffixes":[]},{"propositions":[],"lastnames":["Schurr"],"firstnames":["Erwin"],"suffixes":[]},{"propositions":[],"lastnames":["Cobat"],"firstnames":["Aurélie"],"suffixes":[]}],"month":"March","year":"2021","pmid":"33661925","pages":"e1009392","bibtex":"@article{quistrebert_genome-wide_2021,\n\ttitle = {Genome-wide association study of resistance to {Mycobacterium} tuberculosis infection identifies a locus at 10q26.2 in three distinct populations},\n\tvolume = {17},\n\tissn = {1553-7404},\n\tdoi = {10.1371/journal.pgen.1009392},\n\tabstract = {The natural history of tuberculosis (TB) is characterized by a large inter-individual outcome variability after exposure to Mycobacterium tuberculosis. Specifically, some highly exposed individuals remain resistant to M. tuberculosis infection, as inferred by tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). We performed a genome-wide association study of resistance to M. tuberculosis infection in an endemic region of Southern Vietnam. We enrolled household contacts (HHC) of pulmonary TB cases and compared subjects who were negative for both TST and IGRA (n = 185) with infected individuals (n = 353) who were either positive for both TST and IGRA or had a diagnosis of TB. We found a genome-wide significant locus on chromosome 10q26.2 with a cluster of variants associated with strong protection against M. tuberculosis infection (OR = 0.42, 95\\%CI 0.35-0.49, P = 3.71×10-8, for the genotyped variant rs17155120). 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