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Common genetic variation and the control of HIV-1 in humans.


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.

SUBMITTER: Fellay J 

PROVIDER: S-EPMC2791220 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Common genetic variation and the control of HIV-1 in humans.

Fellay Jacques J   Ge Dongliang D   Shianna Kevin V KV   Colombo Sara S   Ledergerber Bruno B   Cirulli Elizabeth T ET   Urban Thomas J TJ   Zhang Kunlin K   Gumbs Curtis E CE   Smith Jason P JP   Castagna Antonella A   Cozzi-Lepri Alessandro A   De Luca Andrea A   Easterbrook Philippa P   Günthard Huldrych F HF   Mallal Simon S   Mussini Cristina C   Dalmau Judith J   Martinez-Picado Javier J   Miro José M JM   Obel Niels N   Wolinsky Steven M SM   Martinson Jeremy J JJ   Detels Roger R   Margolick Joseph B JB   Jacobson Lisa P LP   Descombes Patrick P   Antonarakis Stylianos E SE   Beckmann Jacques S JS   O'Brien Stephen J SJ   Letvin Norman L NL   McMichael Andrew J AJ   Haynes Barton F BF   Carrington Mary M   Feng Sheng S   Telenti Amalio A   Goldstein David B DB  

PLoS genetics 20091224 12


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  ...[more]

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