title: Tuberculin skin test negativity is under tight genetic control of chromosomal region 11p14-15 in settings with different tuberculosis endemicities.
abstract: A substantial proportion of subjects exposed to a contagious tuberculosis case display lack of tuberculin skin test (TST) reactivity. We previously mapped a major locus (TST1) controlling lack of TST reactivity in families from an area in South Africa where tuberculosis is hyperendemic. Here, we conducted a household tuberculosis contact study in a French area where the endemicity of tuberculosis is low. 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.
authors.affiliation: McGill International TB Centre Department of Human Genetics Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cobat
authors.affiliation: Centre de Lutte Anti-Tuberculeuse, Centre Hospitalier Intercommunal de Créteil, Créteil.
authors.forename: Christine
authors.initials: C
authors.lastname: Poirier
authors.affiliation: Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Eileen
authors.initials: E
authors.lastname: Hoal
authors.affiliation: National Center for Genotyping, Genomic Institute, CEA, Evry.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland-Auge
authors.affiliation: Association Clinique et Thérapeutique Infantile du Val de Marne, Saint Maur des Fossés.
authors.forename: France
authors.initials: F
authors.lastname: de La Rocque
authors.affiliation: Association Clinique et Thérapeutique Infantile du Val de Marne, Saint Maur des Fossés.
authors.forename: François
authors.initials: F
authors.lastname: Corrard
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Grange
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Migaud
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch Howard Hughes Medical Institute, Rockefeller University, New York, New York.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: McGill International TB Centre Department of Human Genetics Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute URC, CIC, Necker, and Cochin Hospitals, Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcaïs
authors.affiliation: Pediatric Pneumology Unit, Necker-Enfants-Malades Hospital, AP-HP.
authors.forename: Christophe
authors.initials: C
authors.lastname: Delacourt
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics*; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013019:South Africa; D014373:Tuberculin / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D014373:Tuberculin
keywords: genome-wide linkage; human genetics; tuberculin skin test; tuberculosis infection