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

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

Journal of Infectious Diseases

ISSN

0022-1899

Publication Date

4-1-2012

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: P_combined = 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.

Volume

205

Issue

7

First Page

1155

Last Page

1162

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

NSUWorks Citation

Limou, Sophie; Olivier Delaneau; Danielle van Manen; Ping An; Efe Sezgin; Sigrid Le Clerc; Cedric Coulonges; Jennifer L. Troyer; Jan H. Veldink; Leonard H. van den Berg; Jean-Louis Spadoni; Lieng Taing; Taoufik Labib; Matthieu Montes; Jean-Francois Delfraissy; Francois Schachter; Stephen J. O'Brien; Susan Buchbinder; Mark Van Natta; Douglas A. Jabs; Philippe Froguel; Hanneke Schuitemaker; Cheryl Winkler; and Jean-Francois Zagury. 2012. "Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition." Journal of Infectious Diseases 205, (7): 1155-1162. https://nsuworks.nova.edu/cnso_bio_facarticles/432