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

Jacques Fellay; Dongliang Ge; Kevin V. Shianna; Sara Colombo; Bruno Ledergerber; Elizabeth T. Cirulli; Thomas J. Urban; Kunlin Zhang; Curtis E. Gumbs; Jason P. Smith; Antonella Castagna; Alessandro Cozzi-Lepri; Andrea De Luca; Philippa Easterbrook; Huldrych F. Günthard; Simon Mallal; Cristina Mussini; Judith Dalmau; Javier Martinez-Picado; José M. Miro; Niels Obel; Steven M. Wolinsky; Jeremy J. Martinson; Roger Detels; Joseph B. Margolick; Lisa P. 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

doi:10.1371/journal.pgen.1000791

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

Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas J. Urban, Kunlin Zhang, Curtis E. Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Huldrych F. Günthard, Simon Mallal, Cristina Mussini, Judith Dalmau, Javier Martinez-Picado, José M. MiroNiels Obel, Steven M. Wolinsky, Jeremy J. Martinson, Roger Detels, Joseph B. Margolick, Lisa P. 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

Bloomberg School of Public Health

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304 Scopus citations

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.

Original language	English (US)
Article number	1000791
Journal	PLoS genetics
Volume	5
Issue number	12
DOIs	https://doi.org/10.1371/journal.pgen.1000791
State	Published - Dec 2009

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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Fellay, J., Ge, D., Shianna, K. V., Colombo, S., Ledergerber, B., Cirulli, E. T., Urban, T. J., Zhang, K., Gumbs, C. E., Smith, J. P., Castagna, A., Cozzi-Lepri, A., De Luca, A., Easterbrook, P., Günthard, H. F., Mallal, S., Mussini, C., Dalmau, J., Martinez-Picado, J., ... Goldstein, D. B. (2009). Common genetic variation and the control of HIV-1 in humans. PLoS genetics, 5(12), Article 1000791. https://doi.org/10.1371/journal.pgen.1000791

Fellay, J, Ge, D, Shianna, KV, Colombo, S, Ledergerber, B, Cirulli, ET, Urban, TJ, Zhang, K, Gumbs, CE, Smith, JP, Castagna, A, Cozzi-Lepri, A, De Luca, A, Easterbrook, P, Günthard, HF, Mallal, S, Mussini, C, Dalmau, J, Martinez-Picado, J, Miro, JM, Obel, N, Wolinsky, SM, Martinson, JJ, Detels, R, Margolick, JB , Jacobson, LP, Descombes, P, Antonarakis, SE, Beckmann, JS, O'Brien, SJ, Letvin, NL, McMichael, AJ, Haynes, BF, Carrington, M, Feng, S, Telenti, A & Goldstein, DB 2009, 'Common genetic variation and the control of HIV-1 in humans', PLoS genetics, vol. 5, no. 12, 1000791. https://doi.org/10.1371/journal.pgen.1000791

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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.",

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AU - Cirulli, Elizabeth T.

AU - Urban, Thomas J.

AU - Zhang, Kunlin

AU - Gumbs, Curtis E.

AU - Smith, Jason P.

AU - Castagna, Antonella

AU - Cozzi-Lepri, Alessandro

AU - De Luca, Andrea

AU - Easterbrook, Philippa

AU - Günthard, Huldrych F.

AU - Mallal, Simon

AU - Mussini, Cristina

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AU - Martinez-Picado, Javier

AU - Miro, José M.

AU - Obel, Niels

AU - Wolinsky, Steven M.

AU - Martinson, Jeremy J.

AU - Detels, Roger

AU - Margolick, Joseph B.

AU - Jacobson, Lisa P.

AU - Descombes, Patrick

AU - Antonarakis, Stylianos E.

AU - Beckmann, Jacques S.

AU - O'Brien, Stephen J.

AU - Letvin, Norman L.

AU - McMichael, Andrew J.

AU - Haynes, Barton F.

AU - Carrington, Mary

AU - Feng, Sheng

AU - Telenti, Amalio

AU - Goldstein, David B.

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

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