Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus
| Autor: | Gregory D. Kirk, Raymond T. Chung, Priya Duggal, Alessandra Mangia, David L. Thomas, Margaret A. Taub, Brian R. Edlin, Rachel Latanich, Chloe L. Thio, Edward L. Murphy, Salim I. Khakoo, Alex H. Kral, Graeme J.M. Alexander, Thomas R. O'Brien, Hugo R. Rosen, Valeria Piazzolla, Sharyne M. Donfield, Shruti H. Mehta, James J. Goedert, Georg M. Lauer, Marion G. Peters, Arthur Y. Kim, Eric O. Johnson, Michael P. Busch, Andrea L. Cox, Matthew E. Cramp, Ana Valencia, Candelaria Vergara, Genevieve L. Wojcik, Laurent Alric |
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| Přispěvatelé: | Johns Hopkins University (JHU), Research Triangle Institute International (RTI International), National Institutes of Health [Bethesda] (NIH), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University School of Medicine [Baltimore], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), University of California (UC), University of Southampton, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SUNY Downstate Medical Center, State University of New York (SUNY), University College London Hospitals (UCLH), University of Colorado [Colorado Springs] (UCCS), Stanford University, University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Linkage disequilibrium [SDV]Life Sciences [q-bio] Remission Spontaneous Genome-wide association study Hepacivirus medicine.disease_cause Hepatitis Receptors G-Protein-Coupled Major Histocompatibility Complex 0302 clinical medicine Genotype Receptors MESH: Interleukins / genetics Medicine GWAS MESH: Interferons Liver Disease Gastroenterology virus diseases Hispanic or Latino Blacks Viral Load Hepatitis C 3. Good health Infectious Diseases Host-Pathogen Interactions MESH: Major Histocompatibility Complex / genetics MESH: African Continental Ancestry Group / genetics 030211 gastroenterology & hepatology Female Infection MESH: Viral Load Risk MESH: European Continental Ancestry Group / genetics Remission Hepatitis C virus Chronic Liver Disease and Cirrhosis Clinical Sciences MESH: Hepatitis C / diagnosis Black People SNP Single-nucleotide polymorphism White People Article Paediatrics and Reproductive Medicine 03 medical and health sciences G-Protein-Coupled Hepatitis - C MESH: Hepacivirus / physiology Genetics Humans 1000 Genomes Project Cytokine MESH: Hepatitis C / ethnology MESH: Humans Hepatology Gastroenterology & Hepatology business.industry Whites Spontaneous Interleukins MESH: Remission Spontaneous Human Genome MESH: Host-Pathogen Interactions MESH: Receptors G-Protein-Coupled / genetics Neurosciences MESH: Hepatitis C / genetics Odds ratio MESH: Hispanic Americans / genetics United States digestive system diseases MESH: Male MESH: United States / epidemiology 030104 developmental biology Emerging Infectious Diseases Good Health and Well Being MESH: Hepatitis C / virology Immunology MESH: Genome-Wide Association Study Interferons business Digestive Diseases MESH: Female Genome-Wide Association Study |
| Zdroj: | Gastroenterology Gastroenterology, 2019, 156 (5), pp.1496-1507.e7. ⟨10.1053/j.gastro.2018.12.014⟩ Gastroenterology, WB Saunders, 2019, 156 (5), pp.1496-1507.e7. ⟨10.1053/j.gastro.2018.12.014⟩ Gastroenterology, vol 156, iss 5 |
| ISSN: | 0016-5085 1528-0012 |
| DOI: | 10.1053/j.gastro.2018.12.014⟩ |
| Popis: | Background & aimsSpontaneous 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.MethodsWe 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.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P= 5.99× 10-50) and the MHC locus 6p21.32 (P= 1.15× 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P= 1.80× 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn 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. |
| Databáze: | OpenAIRE |
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