1. Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition.
- Author
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Limou, Sophie, Delaneau, Olivier, van Manen, Daniëlle, An, Ping, Sezgin, Efe, Clerc, Sigrid Le, Coulonges, Cédric, Troyer, Jennifer L., Veldink, Jan H., van den Berg, Leonard H., Spadoni, Jean-Louis, Taing, Lieng, Labib, Taoufik, Montes, Matthieu, Delfraissy, Jean-François, Schachter, François, O'Brien, Stephen J., Buchbinder, Susan, van Natta, Mark L., and Jabs, Douglas A.
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HIV infections , *HIV , *GENETIC mutation , *META-analysis , *CHEMOKINE receptors , *DISEASE susceptibility , *HIV-positive persons , *SINGLE nucleotide polymorphisms - Abstract
Background. To date, onlymutations 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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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