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

Publication

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

Journal Paper/Review - Oct 29, 2013

Bartha István, 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, Klimkait Thomas, Vernazza Pietro, Bernasconi Enos, 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, Fellay Jacques

Citation

Bartha I, Yerly S, O'Brien S, Listgarten J, Pfeifer N, Lippert C, Fusi N, Kutalik Z, Allen T, Müller V, Harrigan P, Heckerman D, Telenti A, Klimkait T, Vernazza P, Bernasconi E, Carlson J, Brumme C, McLaren P, Brumme Z, John M, Haas D, Martinez-Picado J, Dalmau J, López-Galíndez C, Casado C, Rauch A, Günthard H, Fellay J. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. Elife 2013; 2:e01123.

Type

Journal Paper/Review (English)

Journal

Elife 2013; 2

Publication Date

Oct 29, 2013

Issn Electronic

2050-084X

Pages

e01123

Brief description/objective

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.