Biology Faculty Articles

Title

Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

Authors

Sophie Limou, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France; National Cancer Institute at Frederick
Olivier Delaneau, Conservatoire National des Arts et Metiers - Paris, France
Danielle van Manen, University of Amsterdam - The Netherlands
Ping An, National Cancer Institute at Frederick
Efe Sezgin, National Cancer Institute at Frederick
Sigrid Le Clerc, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France
Cedric Coulonges, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France
Jennifer L. Troyer, National Cancer Institute at Frederick
Jan H. Veldink, University Medical Center- Utrecht, the Netherlands
Leonard H. van den Berg, University Medical Center- Utrecht, the Netherlands
Jean-Louis Spadoni, Conservatoire National des Arts et Metiers - Paris, France
Lieng Taing, Conservatoire National des Arts et Metiers - Paris, France
Taoufik Labib, Conservatoire National des Arts et Metiers - Paris, France
Matthieu Montes, Conservatoire National des Arts et Metiers - Paris, France
Jean-Francois Delfraissy, ANRS Genomic Group - Paris, France
Francois Schachter, Conservatoire National des Arts et Metiers - Paris, France
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Susan Buchbinder, San Francisco Department of Public Health
Mark Van Natta, Johns Hopkins University
Douglas A. Jabs, Mount Sinai School of Medicine; Johns Hopkins University
Philippe Froguel, Institut Pasteur de Lille - France; Imperial College London - United Kingdom
Hanneke Schuitemaker, University of Amsterdam - The Netherlands
Cheryl Winkler, National Cancer Institute at Frederick
Jean-Francois Zagury, Conservatoire National des Arts et Metiers - Paris, France; ANRS Genomic Group - Paris, France

Document Type

Article

Publication Date

4-1-2012

Publication Title

Journal of Infectious Diseases

ISSN

0022-1899

Volume

205

Issue/No.

7

First Page

1155

Last Page

1162

Abstract

Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility.

Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10−5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent.

Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10−8.

Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside theCCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.

Comments

©The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Additional Comments

National Cancer Institute contract #: HHSN26120080001E; National Eye Institute agreement #s: U10 EY 08052, U10 EY 08057, U10 EY 08067

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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