A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
Bartha, I., Carlson, J.M., Brumme, C.J., McLaren, P.J., Brumme, Z.L., John, M., Haas, D.W., Martinez-Picado, J., Dalmau, J., Lopez-Galindez, C., Casado, C., Rauch, A., Günthard, H.F., Bernasconi, E., Vernazza, P., Klimkait, T., Yerly, S., O'Brien, S.J., Listgarten, J., Pfeifer, N., Lippert, C., Fusi, N., Kutalik, Z., Allen, T.M., Muller, V., Harrigan, P.R., Heckerman, D., Telenti, A. and Fellay, J. (2013) A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife, 2 . e01123-e01123.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||eLife Sciences Publications|
|Copyright:||2013 Bartha et al.|
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