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

Fellay, J; Ge, DL; Shianna, KV; Colombo, S; Ledergerber, B; Cirulli, ET; Urban, TJ; ... NIAID Ctr HIV AIDS Vaccine Immunol, ; + view all (2009) Common Genetic Variation and the Control of HIV-1 in Humans. PLOS GENET , 5 (12) , Article e1000791. 10.1371/journal.pgen.1000791. Green open access

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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.

Type: Article
Title: Common Genetic Variation and the Control of HIV-1 in Humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1000791
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1000791
Language: English
Additional information: 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. Funding: Funding was provided by the NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) grant AI067854. This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. AT and SEA are supported by the Swiss National Science Foundation and by the Infectigen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: GENOME-WIDE ASSOCIATION, HLA-C, HOST GENETICS, INFECTION, AIDS, PROGRESSION, DISEASE, POLYMORPHISM, RESISTANCE, HCP5
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/141353
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