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| Item Type: | Article |
|---|---|
| Title: | A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control |
| Creators: |
Bartha, I., Carlson, J.M., Brumme, C.J.  ORCID: https://orcid.org/0000-0003-2722-5288, McLaren, P.J., Brumme, Z.L., John, M., Haas, D.W., Martinez-Picado, J. ORCID: https://orcid.org/0000-0002-4916-2129, Dalmau, J., López-Galíndez, C. ORCID: https://orcid.org/0000-0002-2324-9584, Casado, C., Rauch, A., Günthard, H.F. ORCID: https://orcid.org/0000-0002-1142-6723, Bernasconi, E., Vernazza, P., Klimkait, T., Yerly, S., O'Brien, S.J. ORCID: https://orcid.org/0000-0001-7353-8301, Listgarten, J., Pfeifer, N. ORCID: https://orcid.org/0000-0002-4647-8566, Lippert, C. ORCID: https://orcid.org/0000-0001-6363-2556, Fusi, N., Kutalik, Z., Allen, T.M., Müller, V. ORCID: https://orcid.org/0000-0001-8212-4880, Harrigan, P.R., Heckerman, D., Telenti, A. and Fellay, J. ORCID: https://orcid.org/0000-0002-8240-939X
|
| 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. |
| Keywords: | Alleles, Genome-Wide Association Study, HIV Infections, HIV-1, Histocompatibility Antigens Class I, Host-Pathogen Interactions, Human Genome, Single Nucleotide Polymorphism, Viral Genome, Viral Load |
| Source: | eLife |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications |
| Volume: | 2 |
| Page Range: | e01123 |
| Date: | 29 October 2013 |
| Official Publication: | https://doi.org/10.7554/eLife.01123 |
| PubMed: | View item in PubMed |
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