Major Loci on Chromosomes 8q and 3q Control Interferon γ Production Triggered by Bacillus Calmette-Guerin and 6-kDa Early Secretory Antigen Target, Respectively, in Various Populations. Jabot-Hanin, F., Cobat, A., Feinberg, J., Grange, G., Remus, N., Poirier, C., Boland-Auge, A., Besse, C., Bustamante, J., Boisson-Dupuis, S., Casanova, J., Schurr, E., Alcaïs, A., Hoal, E. G., Delacourt, C., & Abel, L. The Journal of Infectious Diseases, 213(7):1173–1179, April, 2016. 00002 doi abstract bibtex BACKGROUND: Interferon γ (IFN-γ) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown. METHODS: We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified. RESULTS: We identified a major locus on chromosome 8q controlling IFN-γ production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 × 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-γ levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-γ production shared with that induced by BCG (LOD score, 3.72; P = 1.8 × 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. These loci differ from those previously identified as controlling the response to the tuberculin skin test (TST1 and TST2) and the production of TNF-α (TNF1). CONCLUSIONS: The identification of 2 new linkage signals in populations of various ethnic origins living in different M. tuberculosis exposure settings provides new clues about the genetic control of human antimycobacterial immunity.
@article{jabot-hanin_major_2016,
title = {Major {Loci} on {Chromosomes} 8q and 3q {Control} {Interferon} γ {Production} {Triggered} by {Bacillus} {Calmette}-{Guerin} and 6-{kDa} {Early} {Secretory} {Antigen} {Target}, {Respectively}, in {Various} {Populations}},
volume = {213},
issn = {1537-6613},
doi = {10.1093/infdis/jiv757},
abstract = {BACKGROUND: Interferon γ (IFN-γ) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown.
METHODS: We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified.
RESULTS: We identified a major locus on chromosome 8q controlling IFN-γ production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 × 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-γ levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-γ production shared with that induced by BCG (LOD score, 3.72; P = 1.8 × 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. These loci differ from those previously identified as controlling the response to the tuberculin skin test (TST1 and TST2) and the production of TNF-α (TNF1).
CONCLUSIONS: The identification of 2 new linkage signals in populations of various ethnic origins living in different M. tuberculosis exposure settings provides new clues about the genetic control of human antimycobacterial immunity.},
language = {eng},
number = {7},
journal = {The Journal of Infectious Diseases},
author = {Jabot-Hanin, Fabienne and Cobat, Aurélie and Feinberg, Jacqueline and Grange, Ghislain and Remus, Natascha and Poirier, Christine and Boland-Auge, Anne and Besse, Céline and Bustamante, Jacinta and Boisson-Dupuis, Stéphanie and Casanova, Jean-Laurent and Schurr, Erwin and Alcaïs, Alexandre and Hoal, Eileen G. and Delacourt, Christophe and Abel, Laurent},
month = apr,
year = {2016},
pmid = {26690346},
pmcid = {PMC4779307},
note = {00002 },
keywords = {Antigens, Bacterial, Bacterial Proteins, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 8, Cohort Studies, Female, France, Gene Expression Regulation, Bacterial, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Interferon-gamma, Male, Mycobacterium bovis, Phenotype, Prospective Studies, South Africa, Tuberculosis, genetic control, genetic linkage analysis, interferon gamma release assays, mycobacteria},
pages = {1173--1179},
}
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G.","Delacourt, C.","Abel, L."],"year":2016,"bibtype":"article","biburl":"http://bibbase.org/zotero/TBHostGen","bibdata":{"bibtype":"article","type":"article","title":"Major Loci on Chromosomes 8q and 3q Control Interferon γ Production Triggered by Bacillus Calmette-Guerin and 6-kDa Early Secretory Antigen Target, Respectively, in Various Populations","volume":"213","issn":"1537-6613","doi":"10.1093/infdis/jiv757","abstract":"BACKGROUND: Interferon γ (IFN-γ) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown. METHODS: We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified. RESULTS: We identified a major locus on chromosome 8q controlling IFN-γ production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 × 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-γ levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-γ production shared with that induced by BCG (LOD score, 3.72; P = 1.8 × 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. These loci differ from those previously identified as controlling the response to the tuberculin skin test (TST1 and TST2) and the production of TNF-α (TNF1). CONCLUSIONS: The identification of 2 new linkage signals in populations of various ethnic origins living in different M. tuberculosis exposure settings provides new clues about the genetic control of human antimycobacterial immunity.","language":"eng","number":"7","journal":"The Journal of Infectious Diseases","author":[{"propositions":[],"lastnames":["Jabot-Hanin"],"firstnames":["Fabienne"],"suffixes":[]},{"propositions":[],"lastnames":["Cobat"],"firstnames":["Aurélie"],"suffixes":[]},{"propositions":[],"lastnames":["Feinberg"],"firstnames":["Jacqueline"],"suffixes":[]},{"propositions":[],"lastnames":["Grange"],"firstnames":["Ghislain"],"suffixes":[]},{"propositions":[],"lastnames":["Remus"],"firstnames":["Natascha"],"suffixes":[]},{"propositions":[],"lastnames":["Poirier"],"firstnames":["Christine"],"suffixes":[]},{"propositions":[],"lastnames":["Boland-Auge"],"firstnames":["Anne"],"suffixes":[]},{"propositions":[],"lastnames":["Besse"],"firstnames":["Céline"],"suffixes":[]},{"propositions":[],"lastnames":["Bustamante"],"firstnames":["Jacinta"],"suffixes":[]},{"propositions":[],"lastnames":["Boisson-Dupuis"],"firstnames":["Stéphanie"],"suffixes":[]},{"propositions":[],"lastnames":["Casanova"],"firstnames":["Jean-Laurent"],"suffixes":[]},{"propositions":[],"lastnames":["Schurr"],"firstnames":["Erwin"],"suffixes":[]},{"propositions":[],"lastnames":["Alcaïs"],"firstnames":["Alexandre"],"suffixes":[]},{"propositions":[],"lastnames":["Hoal"],"firstnames":["Eileen","G."],"suffixes":[]},{"propositions":[],"lastnames":["Delacourt"],"firstnames":["Christophe"],"suffixes":[]},{"propositions":[],"lastnames":["Abel"],"firstnames":["Laurent"],"suffixes":[]}],"month":"April","year":"2016","pmid":"26690346","pmcid":"PMC4779307","note":"00002 ","keywords":"Antigens, Bacterial, Bacterial Proteins, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 8, Cohort Studies, Female, France, Gene Expression Regulation, Bacterial, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Interferon-gamma, Male, Mycobacterium bovis, Phenotype, Prospective Studies, South Africa, Tuberculosis, genetic control, genetic linkage analysis, interferon gamma release assays, mycobacteria","pages":"1173–1179","bibtex":"@article{jabot-hanin_major_2016,\n\ttitle = {Major {Loci} on {Chromosomes} 8q and 3q {Control} {Interferon} γ {Production} {Triggered} by {Bacillus} {Calmette}-{Guerin} and 6-{kDa} {Early} {Secretory} {Antigen} {Target}, {Respectively}, in {Various} {Populations}},\n\tvolume = {213},\n\tissn = {1537-6613},\n\tdoi = {10.1093/infdis/jiv757},\n\tabstract = {BACKGROUND: Interferon γ (IFN-γ) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown.\nMETHODS: We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified.\nRESULTS: We identified a major locus on chromosome 8q controlling IFN-γ production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 × 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-γ levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-γ production shared with that induced by BCG (LOD score, 3.72; P = 1.8 × 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. 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