Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

Black People / genetics Female Genome-Wide Association Study Hepacivirus / physiology Hepatitis C / diagnosis Hispanic or Latino / genetics Host-Pathogen Interactions Humans Interferons Interleukins / genetics Major Histocompatibility Complex / genetics Male Receptors, G-Protein-Coupled / genetics Remission, Spontaneous United States / epidemiology Viral Load White People / genetics
Cytokine GWAS Risk SNP

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
Apr 2019
Historique:
received: 24 10 2018
revised: 05 12 2018
accepted: 19 12 2018
pubmed: 30 12 2018
medline: 6 5 2019
entrez: 30 12 2018
Statut: ppublish

Résumé

Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry. We performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed. In the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10 In a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.
METHODS METHODS
We performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.
RESULTS RESULTS
In the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10
CONCLUSIONS CONCLUSIONS
In a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

Identifiants

DOI: 10.1053/j.gastro.2018.12.014 PMID: 30593799 PMC: PMC6788806
pubmed: 30593799
pii: S0016-5085(18)35421-0
doi: 10.1053/j.gastro.2018.12.014
pmc: PMC6788806
mid: NIHMS1517446
pii:
doi:

Substances chimiques

interferon-lambda, human 0
IFNL4 protein, human 0
Interleukins 0
Receptors, G-Protein-Coupled 0
Interferons 9008-11-1

Types de publication

Comparative Study Journal Article Meta-Analysis Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1496-1507.e7

Subventions

Organisme : NIDA NIH HHS
ID : R37 DA004334
Pays : United States
Organisme : NIDA NIH HHS
ID : R56 DA004334
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI034989
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI082630
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL076902
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD041224
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI131314
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035043
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA012568
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035040
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035039
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035042
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA036297
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025005
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI031834
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA033541
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024996
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035004
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA013324
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA021550
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA004334
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035041
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA016159
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI034994
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI066345
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146201
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI034993
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD032632
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI042590
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI088791
Pays : United States

Informations de copyright

Copyright © 2019. Published by Elsevier Inc.

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Auteurs

Candelaria Vergara (C)

Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Chloe L Thio (CL)

Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Eric Johnson (E)

Research Triangle Institute International, Research Triangle Park, North Carolina; Atlanta, Georgia; San Francisco, California.

Alex H Kral (AH)

Research Triangle Institute International, Research Triangle Park, North Carolina; Atlanta, Georgia; San Francisco, California.

Thomas R O'Brien (TR)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

James J Goedert (JJ)

Liver Unit Istituto Di Ricovero e Cura a Carattere Scientifico "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

Alessandra Mangia (A)

Liver Unit Istituto Di Ricovero e Cura a Carattere Scientifico "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

Valeria Piazzolla (V)

Liver Unit Istituto Di Ricovero e Cura a Carattere Scientifico "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

Shruti H Mehta (SH)

Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.

Gregory D Kirk (GD)

Johns Hopkins University, School of Medicine, Baltimore, Maryland; Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.

Arthur Y Kim (AY)

Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Georg M Lauer (GM)

Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Raymond T Chung (RT)

Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Andrea L Cox (AL)

Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Marion G Peters (MG)

Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Francisco, California.

Salim I Khakoo (SI)

University of Southampton, Southampton General Hospital, Southampton, UK.

Laurent Alric (L)

Department of Internal Medicine and Digestive Diseases, Centre Hospitalier Universitaire Purpan, UMR 152, Institut de Recherche pour le Développement Toulouse 3 University, France.

Matthew E Cramp (ME)

South West Liver Unit, Plymouth, UK.

Sharyne M Donfield (SM)

Rho, Inc, Chapel Hill, North Carolina.

Brian R Edlin (BR)

State University of New York Downstate College of Medicine, Brooklyn, New York.

Michael P Busch (MP)

University of California and Vitalant Research Institute, San Francisco, California.

Graeme Alexander (G)

University College London Institute for Liver and Digestive Health, The Royal Free Hospital, London, UK.

Hugo R Rosen (HR)

University of Colorado, Aurora, Colorado.

Edward L Murphy (EL)

University of California and Vitalant Research Institute, San Francisco, California.

Rachel Latanich (R)

Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Genevieve L Wojcik (GL)

Department of Genetics, Stanford University School of Medicine, Stanford, California.

Margaret A Taub (MA)

Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.

Ana Valencia (A)

Johns Hopkins University, School of Medicine, Baltimore, Maryland; Universidad Pontificia Bolivariana, Medellin, Colombia.

David L Thomas (DL)

Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Priya Duggal (P)

Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland. Electronic address: pduggal@jhu.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Noirs › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Flaviviridae › Hepacivirus › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Hépatite › Hépatites virales humaines › Hépatite C › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Hispanique ou Latino › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Phénomènes du système immunitaire › Phénomènes immunogénétiques › Complexe majeur d'histocompatibilité › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Phénomènes biologiques › Rémission spontanée › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Nord › États-Unis › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Charge virale › Multi-Ancestry Genome-Wide Association Study...
questionsmedicales.fr › Personnes › Blancs › Multi-Ancestry Genome-Wide Association Study...