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A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

2013; eLife Sciences Publications Ltd; Volume: 2; Linguagem: Inglês

10.7554/elife.01123

2050-084X

István Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. McLaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martínez‐Picado, Judith Dalmau, Cecilio López-Galı́ndez, Concha Casado, Andri Rauch, Huldrych F. Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O’Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolò Fusi, Zoltán Kutalik, Todd M. Allen, Viktor Müller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay,

Genomic variations and chromosomal abnormalities

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.