TY - JOUR TI - A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control AU - Bartha, István AU - Carlson, Jonathan M AU - Brumme, Chanson J AU - McLaren, Paul J AU - Brumme, Zabrina L AU - John, Mina AU - Haas, David W AU - Martinez-Picado, Javier AU - Dalmau, Judith AU - López-Galíndez, Cecilio AU - Casado, Concepción AU - Rauch, Andri AU - Günthard, Huldrych F AU - Bernasconi, Enos AU - Vernazza, Pietro AU - Klimkait, Thomas AU - Yerly, Sabine AU - O’Brien, Stephen J AU - Listgarten, Jennifer AU - Pfeifer, Nico AU - Lippert, Christoph AU - Fusi, Nicolo AU - Kutalik, Zoltán AU - Allen, Todd M AU - Müller, Viktor AU - Harrigan, P Richard AU - Heckerman, David AU - Telenti, Amalio AU - Fellay, Jacques A2 - McVean, Gil VL - 2 PY - 2013 DA - 2013/10/29 SP - e01123 C1 - eLife 2013;2:e01123 DO - 10.7554/eLife.01123 UR - https://doi.org/10.7554/eLife.01123 AB - 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. KW - human genomics KW - HIV KW - viral mutation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -