A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

István Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. McLaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio López-Galíndez, Concepción Casado, Andri Rauch, Huldrych F. Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico PfeiferChristoph Lippert, Nicolo Fusi, Zoltán Kutalik, Todd M. Allen, V. Müller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay

Research output: Contribution to journalArticle

57 Citations (Scopus)

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-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.

Original languageEnglish
Article numbere01123
JournaleLife
Volume2013
Issue number2
DOIs
Publication statusPublished - Oct 29 2013

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Medical Genetics
HIV-1
Genes
Viral Load
Genome
Pathogens
Host Factor 1 Protein
Single Nucleotide Polymorphism
Testing
Polymorphism
Host-Pathogen Interactions
Viral Structures
Genome-Wide Association Study
Plasmas
Amino Acids
DNA
Phenotype
Pressure
Population

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Bartha, I., Carlson, J. M., Brumme, C. J., McLaren, P. J., Brumme, Z. L., John, M., ... Fellay, J. (2013). A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife, 2013(2), [e01123]. https://doi.org/10.7554/eLife.01123

A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. / Bartha, István; Carlson, Jonathan M.; Brumme, Chanson J.; McLaren, Paul J.; Brumme, Zabrina L.; John, Mina; Haas, David W.; Martinez-Picado, Javier; Dalmau, Judith; López-Galíndez, Cecilio; Casado, Concepción; Rauch, Andri; Günthard, Huldrych F.; Bernasconi, Enos; Vernazza, Pietro; Klimkait, Thomas; Yerly, Sabine; O'Brien, Stephen J.; Listgarten, Jennifer; Pfeifer, Nico; Lippert, Christoph; Fusi, Nicolo; Kutalik, Zoltán; Allen, Todd M.; Müller, V.; Richard Harrigan, P.; Heckerman, David; Telenti, Amalio; Fellay, Jacques.

In: eLife, Vol. 2013, No. 2, e01123, 29.10.2013.

Research output: Contribution to journalArticle

Bartha, I, Carlson, JM, Brumme, CJ, McLaren, PJ, Brumme, ZL, John, M, Haas, DW, Martinez-Picado, J, Dalmau, J, López-Galíndez, C, Casado, C, Rauch, A, Günthard, HF, Bernasconi, E, Vernazza, P, Klimkait, T, Yerly, S, O'Brien, SJ, Listgarten, J, Pfeifer, N, Lippert, C, Fusi, N, Kutalik, Z, Allen, TM, Müller, V, Richard Harrigan, P, Heckerman, D, Telenti, A & Fellay, J 2013, 'A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control', eLife, vol. 2013, no. 2, e01123. https://doi.org/10.7554/eLife.01123
Bartha, István ; Carlson, Jonathan M. ; Brumme, Chanson J. ; McLaren, Paul J. ; Brumme, Zabrina L. ; John, Mina ; Haas, David W. ; Martinez-Picado, Javier ; Dalmau, Judith ; López-Galíndez, Cecilio ; Casado, Concepción ; Rauch, Andri ; Günthard, Huldrych F. ; Bernasconi, Enos ; Vernazza, Pietro ; Klimkait, Thomas ; Yerly, Sabine ; O'Brien, Stephen J. ; Listgarten, Jennifer ; Pfeifer, Nico ; Lippert, Christoph ; Fusi, Nicolo ; Kutalik, Zoltán ; Allen, Todd M. ; Müller, V. ; Richard Harrigan, P. ; Heckerman, David ; Telenti, Amalio ; Fellay, Jacques. / A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. In: eLife. 2013 ; Vol. 2013, No. 2.
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