Bartha, IstvánCarlson, Jonathan MBrumme, Chanson JMcLaren, Paul JBrumme, Zabrina LJohn, MinaHaas, David WMartinez-Picado, JavierDalmau, JudithLópez-Galíndez, CecilioCasado, ConcepciónRauch, AndriGünthard, Huldrych FBernasconi, EnosVernazza, PietroKlimkait, ThomasYerly, SabineO’Brien, Stephen JListgarten, JenniferPfeifer, NicoLippert, ChristophFusi, NicoloKutalik, ZoltánAllen, ToddMüller, ViktorHarrigan, P RichardHeckerman, DavidTelenti, AmalioFellay, Jacques2014-03-102013Bartha, I., J. M. Carlson, C. J. Brumme, P. J. McLaren, Z. L. Brumme, M. John, D. W. Haas, et al. 2013. “A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.” eLife 2 (1): e01123. doi:10.7554/eLife.01123. http://dx.doi.org/10.7554/eLife.01123.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11878911HIV-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.01123.001en-UShuman genomicsHIVviral mutationsHumanJournal Article2014-03-1010.7554/eLife.01123