Association Study of Common Genetic Variants and HIV- 1 Acquisition in 6,300 Infected Cases and 7,200 Controls

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

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

PLoS Pathogens

ISSN

1553-7366

Publication Date

7-25-2013

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.

Volume

9

Issue

7 e1003515

First Page

1

Last Page

9

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

NSUWorks Citation

McLaren, Paul J.; Cedric Coulonges; Stephan Ripke; Leonard H. van den Berg; Susan Buchbinder; Mary Carrington; Andrea Cossarizza; Judith Dalmau; Steven G. Deeks; Olivier Delaneau; Andrea De Luca; James J. Goedert; David W. Haas; Joshua T. Herbeck; Sekar Kathiresan; Gregory D. Kirk; Olivier Lambotte; Ma Luo; Simon Mallal; Danielle van Manen; Javier Martinez-Picado; Florencia Pereyra; Francis A. Plummer; Guido Poli; Ying Qi; Pierre Rucart; Manj S. Sandhu; Patrick R. Shea; Hanneke Schuitemaker; Ioannis Theodorou; Fredrik Vannberg; Jan Veldink; Bruce D. Walker; Amy C. Weintrob; Cheryl Winkler; Steven M. Wolinsky; Amalio Telenti; David B. Goldstein; Paul I. W. de Bakker; Jean-Francois Zagury; and Jacques Fellay. 2013. "Association Study of Common Genetic Variants and HIV- 1 Acquisition in 6,300 Infected Cases and 7,200 Controls." PLoS Pathogens 9, (7 e1003515): 1-9. https://nsuworks.nova.edu/cnso_bio_facarticles/742