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A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control
Open accessAbstract
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.
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Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Human metabolic individuality in biomedical and pharmaceutical research
CARDIoGRAM, Suhre, K., Shin, S.-Y., Petersen, A.-K., Mohney, R. P., Meredith, D., Wägele, B., Altmaier, E., Deloukas, P., Erdmann, J., et al. (2011) · Nature · doi:10.1038/nature10354 · Cited by 1,017
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Coscolla, M., & Gagneux, S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.09.012 · Cited by 451
Clinical and biological insights from viral genome sequencing
Houldcroft, C. J., Beale, M. A., & Breuer, J. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.182 · Cited by 334
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Brites, D., & Gagneux, S. (2015) · Immunological Reviews · doi:10.1111/imr.12264 · Cited by 298
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Yan, L. L., Simms, C. L., McLoughlin, F., Vierstra, R. D., & Zaher, H. S. (2019) · Nature Communications · doi:10.1038/s41467-019-13579-3 · Cited by 123
Metadata
- Authors
- Bartha, I., Carlson, J. M., Brumme, C. J., McLaren, P. J., Brumme, Z. L., John, M., Haas, D. W., Martinez-Picado, J., Dalmau, J., López-Galíndez, 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., Müller, V., Harrigan, P. R., Heckerman, D., Telenti, A., Fellay, J., & Study, F. T. H. G.-T.-G. S. A. T. S. H. C.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2013-10-29
- Volume
- 2
- Pages
- e01123-e01123
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2170066264
- Cited by
- 196
- References
- 2
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Bartha, I., Carlson, J. M., Brumme, C. J., McLaren, P. J., Brumme, Z. L., John, M., Haas, D. W., Martinez-Picado, J., Dalmau, J., López-Galíndez, C., Casado, C., Rauch, A., Günthard, H. F., Bernasconi, E., Vernazza, P., Klimkait, T., Yerly, S., O’Brien, S. J., Listgarten, J., . . . Study, F. T. H. G.-T.-G. S. A. T. S. H. C. (2013). A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife. https://doi.org/10.7554/elife.01123
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
