Title

A Genome-To-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control

Authors

Istvan Bartha, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest; Swiss Institute of Bioinformatics
Jonathan M. Carlson, eScience Group
Chanson J. Brumme, 6BC Centre for Excellence in HIV/AIDS - Vancouver, Canada
Paul J. McLaren, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Swiss Institute of Bioinformatics
Zabrina L. Brumme, BC Centre for Excellence in HIV/AIDS - Vancouver, Canada; Simon Fraser University - Canada
Mina John, Murdoch University - Australia
David W. Haas, Vanderbilt University
Javier Martinez-Picado, Universitat Autònoma de Barcelona - Spain; Institució Catalana de Recerca i Estudis Avançats - Barcelona, Spain
Judith Dalmau, Universitat Autònoma de Barcelona - Spain
Cecilio Lopez-Galindez, Instituto de Salud Carlos III - Madrid, Spain
Concepcion Casado, Instituto de Salud Carlos III - Madrid, Spain
Andri Rauch, University of Bern & Inselspital - Switzerland
Huldrych F. Gunthard, University of Zurich - Switzerland
Enos Bernasconi, Regional Hospital of Lugano - Switzerland
Pietro Vernazza, Cantonal Hospital - Switzerland
Thomas Klimkait, University of Basel - Switzerland
Sabine Yerly, Geneva University Hospitals - Switzerland
Stephen J. O'Brien, St. Petersburg State University - RussiaFollow
Jennifer Listgarten, eScience Group
Nico Pfeifer, eScience Group
Christoph Lippert, eScience Group
Nicolo Fusi, eScience Group
Zoltan Kutalik, Swiss Institute of Bioinformatics; University of Lausanne - Switzerland
Todd M. Allen, Massachusetts General Hospital
Viktor Muller, Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest
P. Richard Harrigan, BC Centre for Excellence in HIV/AIDS - Vancouver, Canada; University of British Columbia - Canada
David Heckerman, eScience Group
Amalio Telenti, University of Lausanne - Switzerland
Jacques Fellay, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Swiss Institute of Bioinformatics

Document Type

Article

Publication Date

10-29-2013

Publication Title

eLife

ISSN

2050-084X

Volume

2

Issue/No.

e01123

First Page

1

Last Page

16

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.

Comments

©Copyright Bartha et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Additional Comments

Swiss National Science Foundation grant #s: 33CS30_134277/Swiss HIV Cohort Study, 31003A_132863/1, PP00P3_133703/1; Sciex-NMS Program grant #: 10.267; Spanish Ministry of Science and Innovation grant #: SAF 2007-61036, 2010-17226, 2010-18917; Fundacion para la investigacion y prevencion del SIDA en Espana grant #s: 36558/06, 36641/07, 36779/08, 360766/09; RETIC de Investigacion en SIDA grant #: RD06/006/0036; National Institute of Allergy and Infectious Diseases grant #: P01-AI074415; SNF Professorship grant #: PP00P3_133703/1

NSUWorks Citation

Bartha, Istvan; Jonathan M. Carlson; Chanson J. Brumme; Paul J. McLaren; Zabrina L. Brumme; Mina John; David W. Haas; Javier Martinez-Picado; Judith Dalmau; Cecilio Lopez-Galindez; Concepcion Casado; Andri Rauch; Huldrych F. Gunthard; Enos Bernasconi; Pietro Vernazza; Thomas Klimkait; Sabine Yerly; Stephen J. O'Brien; Jennifer Listgarten; Nico Pfeifer; Christoph Lippert; Nicolo Fusi; Zoltan Kutalik; Todd M. Allen; Viktor Muller; P. Richard Harrigan; David Heckerman; Amalio Telenti; and Jacques Fellay. 2013. "A Genome-To-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control." eLife 2, (e01123): 1-16. https://nsuworks.nova.edu/cnso_bio_facarticles/751

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015