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

The Journal of Infectious Diseases
Sophie LimouJean-François Zagury

Abstract

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. 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. 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). 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 nexu...Continue Reading

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Feb 2, 2013·Genome Biology·Stephen J O'Brien, Sher L Hendrickson
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