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

Research output: Contribution to journalArticle

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 languageEnglish
Article number1000791
JournalPLoS Genetics
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 2009

ASJC Scopus subject areas

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

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  • Cite this

    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), [1000791]. https://doi.org/10.1371/journal.pgen.1000791