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

• Published in: PLoS genetics Vol. 5; no. 12; p. e1000791
• Main Authors: Fellay, Jacques, Ge, Dongliang, Shianna, Kevin V., Colombo, Sara, Ledergerber, Bruno, Cirulli, Elizabeth T., Urban, Thomas J., Zhang, Kunlin, Gumbs, Curtis E., Smith, Jason P., Castagna, Antonella, Cozzi-Lepri, Alessandro, De Luca, Andrea, Easterbrook, Philippa, Günthard, Huldrych F., Mallal, Simon, Mussini, Cristina, Dalmau, Judith, Martinez-Picado, Javier, Miro, José M., Obel, Niels, Wolinsky, Steven M., Martinson, Jeremy J., Detels, Roger, Margolick, Joseph B., Jacobson, Lisa P., Descombes, Patrick, Antonarakis, Stylianos E., Beckmann, Jacques S., O'Brien, Stephen J., Letvin, Norman L., McMichael, Andrew J., Haynes, Barton F., Carrington, Mary, Feng, Sheng, Telenti, Amalio, Goldstein, David B.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2009; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Alleles; Allelomorphism; Disease Progression; Disease transmission; Female; Genes; Genetic Variation; Genetics; Genetics and Genomics/Complex Traits; Genetics and Genomics/Genetics of Disease; Genotype; Genètica molecular; HIV; HIV (Viruses); HIV infection; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunology/Genetics of the Immune System; Infectious Diseases/HIV Infection and AIDS; Kaplan-Meier Estimate; Major Histocompatibility Complex - genetics; Male; Medical research; Molecular genetics; Phenotype; Polymorphism, Single Nucleotide - genetics; Studies; VIH (Virus); Viral Load; Virology/Mechanisms of Resistance and Susceptibility, including Host Genetics
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000791

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.