Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians.

Adult Disease Progression Female Gene Expression Genetic Loci Genome-Wide Association Study Genotype Humans Male Monocytes Mycobacterium tuberculosis / genetics Peru Sodium-Potassium-Exchanging ATPase / genetics Tuberculosis / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 08 2019
Historique:
received: 28 08 2018
accepted: 24 07 2019
entrez: 23 8 2019
pubmed: 23 8 2019
medline: 18 12 2019
Statut: epublish

Résumé

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability ([Formula: see text]) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10

Identifiants

DOI: 10.1038/s41467-019-11664-1 PMID: 31434886 PMC: PMC6704092
pubmed: 31434886
doi: 10.1038/s41467-019-11664-1
pii: 10.1038/s41467-019-11664-1
pmc: PMC6704092
doi:

Substances chimiques

ATP1B3 protein, human 0
Sodium-Potassium-Exchanging ATPase EC 7.2.2.13

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3765

Subventions

Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : Medical Research Council
ID : MR/M012328/1
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U01 HG009379
Pays : United States
Organisme : Medical Research Council
ID : MR/M012328/2
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI076217
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111224
Pays : United States

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Auteurs

Yang Luo (Y)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-7385-6166

Sara Suliman (S)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-5154-576X

Samira Asgari (S)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-2347-8985

Tiffany Amariuta (T)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, 02138, USA.
ORCID: 0000-0003-0121-1726

Yuriy Baglaenko (Y)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Marta Martínez-Bonet (M)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-0715-403X

Kazuyoshi Ishigaki (K)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Maria Gutierrez-Arcelus (M)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-7898-7691

Roger Calderon (R)

Socios En Salud, Lima, Peru.

Leonid Lecca (L)

Socios En Salud, Lima, Peru.

Segundo R León (SR)

Socios En Salud, Lima, Peru.

Judith Jimenez (J)

Socios En Salud, Lima, Peru.

Rosa Yataco (R)

Socios En Salud, Lima, Peru.

Carmen Contreras (C)

Socios En Salud, Lima, Peru.

Jerome T Galea (JT)

School of Social Work, University of South Florida, Tampa, FL, USA.

Mercedes Becerra (M)

Department of Global Health and Social Medicine, and Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Sergey Nejentsev (S)

Department of Medicine, University of Cambridge, Cambridge, UK.
Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, Amsterdam, Netherlands.

Peter A Nigrovic (PA)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.

D Branch Moody (DB)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-2306-3058

Megan B Murray (MB)

Department of Global Health and Social Medicine, and Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. megan.murray.epi@gmail.com.

Soumya Raychaudhuri (S)

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. soumya@broadinstitute.org.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
Arthritis Research UK Centre for Genetics and Genomics, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. soumya@broadinstitute.org.
ORCID: 0000-0002-1901-8265

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Early progression to active tuberculosis is a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Early progression to active tuberculosis is a...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Early progression to active tuberculosis is a...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Early progression to active tuberculosis is a...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Early progression to active tuberculosis is a...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Early progression to active tuberculosis is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Early progression to active tuberculosis is a...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Monocytes › Early progression to active tuberculosis is a...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis › Early progression to active tuberculosis is a...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Sud › Pérou › Early progression to active tuberculosis is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › P-type ATPases › Sodium-Potassium-Exchanging ATPase › Early progression to active tuberculosis is a...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram positif › Infections à Actinomycetales › Infections à Mycobacterium › Tuberculose › Early progression to active tuberculosis is a...