title: Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition.
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 the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.
authors.affiliation: Laboratoire Génomique, Bioinformatique, et Applications, EA4627, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Manen
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Efe
authors.initials: E
authors.lastname: Sezgin
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulonges
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Troyer
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Spadoni
authors.forename: Lieng
authors.initials: L
authors.lastname: Taing
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.forename: Matthieu
authors.initials: M
authors.lastname: Montes
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: François
authors.initials: F
authors.lastname: Schachter
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Mark L
authors.initials: ML
authors.lastname: van Natta
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Jabs
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D000072474:Cytochrome P450 Family 7; D060467:Disease Resistance; D005060:Europe; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013250:Steroid Hydroxylases / Q000235:genetics; D014481:United States
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human