Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7688
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
Bartha, István | Carlson, Jonathan M | Brumme, Chanson J | McLaren, Paul J | Brumme, Zabrina L | John, Mina | Haas, David W | Martinez-Picado, Javier | Dalmau, Judith | Lopez-Galindez, Luis Cecilio ISCIII | Casado, Concepcion ISCIII | Rauch, Andri | Günthard, Huldrych F | Bernasconi, Enos | Vernazza, Pietro | Klimkait, Thomas | Yerly, Sabine | O'Brien, Stephen J | Listgarten, Jennifer | Pfeifer, Nico | Lippert, Christoph | Fusi, Nicolo | Kutalik, Zoltán | Allen, Todd M | Müller, Viktor | Harrigan, P Richard | Heckerman, David | Telenti, Amalio | Fellay, Jacques
Elife. 2013 Oct 29;2:e01123.
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001.
Alleles | Genome-Wide Association Study | HIV Infections | HIV-1 | Histocompatibility Antigens Class I | Host-Pathogen Interactions | Humans | Viral Load | Genome, Human | Genome, Viral | Polymorphism, Single Nucleotide
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