Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition
Journal of Infectious Diseases
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.
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. http://nsuworks.nova.edu/cnso_bio_facarticles/432