Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition

Sophie Limou, Olivier Delaneau, Daniëlle Van Manen, Ping An, Efe Sezgin, Sigrid Le Clerc, Cédric Coulonges, Jennifer L. Troyer, Jan H. Veldink, Leonard H. Van Den Berg, Jean Louis Spadoni, Lieng Taing, Taoufik Labib, Matthieu Montes, Jean François Delfraissy, François Schachter, Stephen J. O'Brien, Susan Buchbinder, Mark L. Van Natta, Douglas A. JabsPhilippe Froguel, Hanneke Schuitemaker, Cheryl A. Winkler, Jean François Zagury

Research output: Contribution to journalArticle

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 the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.

Original languageEnglish (US)
Pages (from-to)1155-1162
Number of pages8
JournalJournal of Infectious Diseases
Volume205
Issue number7
DOIs
StatePublished - Apr 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Limou, S., Delaneau, O., Van Manen, D., An, P., Sezgin, E., Le Clerc, S., Coulonges, C., Troyer, J. L., Veldink, J. H., Van Den Berg, L. H., Spadoni, J. L., Taing, L., Labib, T., Montes, M., Delfraissy, J. F., Schachter, F., O'Brien, S. J., Buchbinder, S., Van Natta, M. L., ... Zagury, J. F. (2012). Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition. Journal of Infectious Diseases, 205(7), 1155-1162. https://doi.org/10.1093/infdis/jis028