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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Bartha István, Carlson Jonathan M, Brumme Chanson J, McLaren Paul J, Brumme Zabrina L, John Mina, Haas David W, Martinez-Picado Javier, Dalmau Judith, López-Galíndez Cecilio, Casado Concepción, 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,
Project Host evolutionary genomics of HIV-1 and other retroviruses
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Original article (peer-reviewed)

Journal eLife
Volume (Issue) 2
Page(s) 01123 - 01123
Title of proceedings eLife
DOI 10.7554/eLife.01123

Open Access

Abstract

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.
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