title: A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
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. DOI:http://dx.doi.org/10.7554/eLife.01123.001.
authors.affiliation: School of Life Sciences , École Polytechnique Fédérale de Lausanne , Lausanne , Switzerland ; Institute of Microbiology , University Hospital and University of Lausanne , Lausanne , Switzerland ; Research Group of Theoretical Biology and Evolutionary Ecology , Eötvös Loránd University and the Hungarian Academy of Sciences , Budapest , Hungary ; Swiss Institute of Bioinformatics , Lausanne , Switzerland.
authors.forename: István
authors.initials: I
authors.lastname: Bartha
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Carlson
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaren
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Mina
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authors.lastname: John
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Judith
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authors.lastname: Dalmau
authors.forename: Cecilio
authors.initials: C
authors.lastname: López-Galíndez
authors.forename: Concepción
authors.initials: C
authors.lastname: Casado
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Jennifer
authors.initials: J
authors.lastname: Listgarten
authors.forename: Nico
authors.initials: N
authors.lastname: Pfeifer
authors.forename: Christoph
authors.initials: C
authors.lastname: Lippert
authors.forename: Nicolo
authors.initials: N
authors.lastname: Fusi
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Viktor
authors.initials: V
authors.lastname: Müller
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
mesh_terms: D000483:Alleles; D015894:Genome, Human; D016679:Genome, Viral; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load / Q000235:genetics* / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I
keywords: HIV; Human; human genomics; viral mutations