Common Genetic Variation and the Control of HIV-1 in Humans

Authors

• Jacques Fellay, Duke University
• Dongliang Ge, Duke University
• Kevin V. Shianna, Duke University
• Sara Colombo, University of Lausanne - Switzerland
• Bruno Ledergerber, University of Zurich - Switzerland
• Elizabeth T. Cirulli, Duke University
• Thomas J. Urban, Duke University
• Kunlin Zhang, University of Lausanne - Switzerland; Chinese Academy of Sciences - Beijing
• Curtis Gumbs, Duke University
• Jason P. Smith, Duke University
• Antonella Castagna, Vita-Salute San Raffaele University and Diagnostica - Milan, Italy; Ricerca San Raffaele - Milan, Italy
• Alessandro Cozzi-Lepri, University College London - United Kingdom
• Andrea de Luca, Catholic University of the Sacred Heart - Rome, Italy
• Philippa Easterbrook, Kings College London - United Kingdom
• Huldrych F. Gunthard, University of Zurich - Switzerland
• Simon Mallal, Murdoch University - Perth, Australia
• Cristina Mussini, Azienda Ospedaliero-Universitaria - Modena, Italy
• Judith Dalmau, IrsiCaixa Foundation; Hospital Germans Trias i Pujol - Badalona, Spain
• Javier Martinez-Picado, IrsiCaixa Foundation; Hospital Germans Trias i Pujol - Badalona, Spain; Institucio Catalana de Recerca i Estudis Avancats - Barcelona, Spain
• Jose M. Miro, University of Barcelona - Spain
• Niels Obel, Copenhagen University - Denmark
• Steven M. Wolinsky, Northwestern University
• Jeremy J. Martinson, University of Pittsburgh
• Roger Detels, University of California - Los Angeles
• Joseph Margolick, Johns Hopkins University
• Lisa Jacobson, Johns Hopkins University
• Patrick Descombes, University of Geneva - Switzerland
• Stylianos E. Antonarakis, University of Geneva - Switzerland
• Jacques S. Beckmann, University of Lausanne - Switzerland; Centre Hospitalier Universitaire Vaudois - Lausanne, Switzerland
• Stephen J. O'Brien, National Cancer Institute at FrederickFollow
• Norman L. Letvin, Harvard Medical School
• Andrew J. McMichael, John Radcliffe Hospital - United Kingdom
• Barton F. Haynes, Duke University
• Mary Carrington, National Cancer Institute at Frederick; Ragon Institute of Massachusetts General Hospital, MIT and Harvard
• Sheng Feng, Duke University
• Amalio Telenti, University of Lausanne - Switzerland
• David B. Goldstein, Duke University
• NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

PLoS ONE

ISSN

1932-6203

Publication Date

12-2009

Abstract

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

Volume

5

Issue

12 e1000791

First Page

1

Last Page

12

Comments

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Additional Comments

CHAVI grant #: AI067854; National Cancer Institute contract #: HHSN261200800001E

NSUWorks Citation

Fellay, Jacques; Dongliang Ge; Kevin V. Shianna; Sara Colombo; Bruno Ledergerber; Elizabeth T. Cirulli; Thomas J. Urban; Kunlin Zhang; Curtis Gumbs; Jason P. Smith; Antonella Castagna; Alessandro Cozzi-Lepri; Andrea de Luca; Philippa Easterbrook; Huldrych F. Gunthard; Simon Mallal; Cristina Mussini; Judith Dalmau; Javier Martinez-Picado; Jose M. Miro; Niels Obel; Steven M. Wolinsky; Jeremy J. Martinson; Roger Detels; Joseph Margolick; Lisa Jacobson; Patrick Descombes; Stylianos E. Antonarakis; Jacques S. Beckmann; Stephen J. O'Brien; Norman L. Letvin; Andrew J. McMichael; Barton F. Haynes; Mary Carrington; Sheng Feng; Amalio Telenti; David B. Goldstein; and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). 2009. "Common Genetic Variation and the Control of HIV-1 in Humans." PLoS ONE 5, (12 e1000791): 1-12. https://nsuworks.nova.edu/cnso_bio_facarticles/766