Biology Faculty Articles

Authors

Paul J. McLaren, Ecole Polytechnique Federale de Lausanne - Switzerland; University Hospital Center and University of Lausanne - Switzerland; Broad Institute of MIT and Harvard
Cedric Coulonges, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France
Stephan Ripke, Broad Institute of MIT and Harvard; Harvard Medical School
Leonard H. van den Berg, University Medical Center- Utrecht, the Netherlands
Susan Buchbinder, San Francisco Department of Public Health
Mary Carrington, National Cancer Institute at Frederick; Ragon Institute of Massachusetts General Hospital, MIT and Harvard
Andrea Cossarizza, University of Modena - Italy
Judith Dalmau, Universitat Autònoma de Barcelona - Spain
Steven G. Deeks, University of California - San Francisco
Olivier Delaneau, University of Oxford - United Kingdom
Andrea De Luca, Siena University Hospital - Italy; Universita Catolica del Sacro Cuore - Roma, Italy
James J. Goedert, National Cancer Institute at Rockville
David W. Haas, Vanderbilt University
Joshua T. Herbeck, University of Washington School of Medicine - Seattle
Sekar Kathiresan, Broad Institute of MIT and Harvard; Harvard Medical School
Gregory D. Kirk, Johns Hopkins University
Olivier Lambotte, INSERM - Bicetre, France; University Paris-Sud - France; Bicetre Hospital - France
Ma Luo, University of Manitoba - Canada; National Microbiology Laboratory - Canada
Simon Mallal, Murdoch University and Pathwest - Perth, Australia
Danielle van Manen, University of Amsterdam - The Netherlands
Javier Martinez-Picado, Universitat Autònoma de Barcelona - Spain; Institució Catalana de Recerca i Estudis Avançats - Barcelona, Spain
Florencia Pereyra, Ragon Institute of MGH, MIT and Harvard; Harvard Medical School
Francis A. Plummer, University of Manitoba; National Microbiology Laboratory - Canada
Guido Poli, San Raffaele University and Scientific Institute - Milano, Italy
Ying Qi, National Cancer Institute at Frederick
Pierre Rucart, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France
Manj S. Sandhu, Wellcome Trust Sanger Institute - United Kingdom; University of Cambridge - United Kingdom
Patrick R. Shea, Duke University
Hanneke Schuitemaker, University of Amsterdam - The Netherlands
Ioannis Theodorou, ANRS Genomic Group - Paris, France; INSERM UMRS - Paris, France
Fredrik Vannberg, Georgia Institute of Technology
Jan Veldink, University Medical Center- Utrecht, the Netherlands
Bruce D. Walker, Ragon Institute of MGH, MIT and Harvard; Howard Hughes Medical Institute
Amy C. Weintrob, Uniformed Services University of the Health Sciences
Cheryl Winkler, National Cancer Institute at Frederick
Steven M. Wolinsky, Northwestern University
Amalio Telenti, University of Lausanne - Switzerland
David B. Goldstein, Duke University
Paul I. W. de Bakker, Broad Institute of MIT and Harvard; Harvard Medical School; University Medical Center Utrecht - The Netherlands
Jean-Francois Zagury, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France
Jacques Fellay, Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland

Document Type

Article

Publication Date

7-25-2013

Publication Title

PLoS Pathogens

ISSN

1553-7366

Volume

9

Issue/No.

7 e1003515

First Page

1

Last Page

9

Abstract

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception ofCCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.

Comments

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Additional Comments

National Cancer Institute contract #: HHSN26120080001E; National Heart, Lung, and Blood Institute grant #: R01 HL087676

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015