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

TitleA genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
Publication TypeJournal Article
Year of Publication2013
AuthorsBartha I, Carlson JM, Brumme CJ, McLaren PJ, Brumme ZL, John M, Haas DW, Martinez-Picado J, Dalmau J, López-Galíndez C, Casado C, Rauch A, Günthard HF, Bernasconi E, Vernazza P, Klimkait T, Yerly S, O'Brien SJ, Listgarten J, Pfeifer N, Lippert C, Fusi N, Kutalik Z, Allen TM, Müller V, P Harrigan R, Heckerman D, Telenti A, Fellay J
JournalElife
Volume2
Paginatione01123
Date Published2013
ISSN2050-084X
KeywordsAlleles, Genome, Human, Genome, Viral, Genome-Wide Association Study, Histocompatibility Antigens Class I, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Polymorphism, Single Nucleotide, Viral Load
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.

DOI10.7554/eLife.01123
Alternate JournalElife
PubMed ID24171102
PubMed Central IDPMC3807812