Bartha, IstvánCarlson, Jonathan MBrumme, Chanson JMcLaren, Paul JBrumme, Zabrina LJohn, MinaHaas, David WMartinez-Picado, JavierDalmau, JudithLopez-Galindez, Luis CecilioCasado, ConcepcionRauch, AndriGünthard, Huldrych FBernasconi, EnosVernazza, PietroKlimkait, ThomasYerly, SabineO'Brien, Stephen JListgarten, JenniferPfeifer, NicoLippert, ChristophFusi, NicoloKutalik, ZoltánAllen, Todd MMüller, ViktorHarrigan, P RichardHeckerman, DavidTelenti, AmalioFellay, Jacques2019-05-282019-05-282013-10-29Elife. 2013 Oct 29;2:e01123.2050-084Xhttp://hdl.handle.net/20.500.12105/7688HIV-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.engVoRhttp://creativecommons.org/licenses/by/4.0/HIVHumanHuman genomicsViral mutationsAllelesGenome-Wide Association StudyHIV InfectionsHIV-1Histocompatibility Antigens Class IHost-Pathogen InteractionsHumansViral LoadGenome, HumanGenome, ViralPolymorphism, Single NucleotideAtribución 4.0 Internacional241711022e0112310.7554/eLife.01123eLifeopen access