title: Genomewide association study of a rapid progression cohort identifies new susceptibility alleles for AIDS (ANRS Genomewide Association Study 03).
abstract: BACKGROUND
  Previous genomewide association studies (GWASs) of AIDS have targeted end points based on the control of viral load and disease nonprogression. The discovery of genetic factors that predispose individuals to rapid progression to AIDS should also reveal new insights into the molecular etiology of the pathology.
  
  
  METHODS
  We undertook a case-control GWAS of a unique cohort of 85 human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced rapid disease progression, using Illumina HumanHap300 BeadChips. The case group was compared with a control group of 1352 individuals for the 291,119 autosomal single-nucleotide polymorphisms (SNPs) passing the quality control tests, using the false-discovery rate (FDR) statistical method for multitest correction.
  
  
  RESULTS
  Novel associations with rapid progression (FDR, < or = 25%) were identified for PRMT6 (P = 6.1 x 10(-7); odds ratio [OR], 0.24), SOX5 (P = 1.8 x 10(-6); OR, 0.45), RXRG (P = 3.9 x 10(-6); OR, 3.29), and TGFBRAP1 (P = 7 x 10(-6); OR, 0.34). The haplotype analysis identified exonic and promoter SNPs potentially important for PRMT6 and TGFBRAP1 function.
  
  
  CONCLUSIONS
  The statistical and biological relevance of these associations and their high ORs underscore the power of extreme phenotypes for GWASs, even with a modest sample size. These genetic results emphasize the role of the transforming growth factor beta pathway in the pathogenesis of HIV-1 disease. Finally, the wealth of information provided by this study should help unravel new diagnostic and therapeutic targets.
authors.affiliation: Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulonges
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Lieng
authors.initials: L
authors.lastname: Taing
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.forename: Rob
authors.initials: R
authors.lastname: Sladek
authors.forename: Christiane
authors.initials: C
authors.lastname: Deveau
authors.forename: Hélène
authors.initials: H
authors.lastname: Guillemain
authors.forename: Rojo
authors.initials: R
authors.lastname: Ratsimandresy
authors.forename: Matthieu
authors.initials: M
authors.lastname: Montes
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Spadoni
authors.forename: Amu
authors.initials: A
authors.lastname: Therwath
authors.forename: François
authors.initials: F
authors.lastname: Schächter
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelièvre
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006679:HIV Seropositivity; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide