Genomewide Association Study of a Rapid Progression Cohort Identifies New Susceptibility Alleles for AIDS (ANRS Genomewide Association Study 03) - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Journal of Infectious Diseases Année : 2009

Genomewide Association Study of a Rapid Progression Cohort Identifies New Susceptibility Alleles for AIDS (ANRS Genomewide Association Study 03)

Olivier Delaneau
Matthieu Montes
Amu Therwath
  • Fonction : Auteur
Yves Levy
  • Fonction : Auteur
  • PersonId : 993190

Résumé

BackgroundPrevious 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 MethodsWe 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 ResultsNovel associations with rapid progression (FDR, ⩽25%) were identified for PRMT6 (P=6.1×10-7; odds ratio [OR], 0.24), SOX5 (P=1.8×10-6; OR, 0.45), RXRG (P=3.9×10-6; OR, 3.29), and TGFBRAP1 (P=7×10-6; OR, 0.34). The haplotype analysis identified exonic and promoter SNPs potentially important for PRMT6 and TGFBRAP1 function ConclusionsThe 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 β 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

Dates et versions

hal-02566721 , version 1 (07-05-2020)

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Citer

Sigrid Le Clerc, Sophie Limou, Cédric Coulonges, Wassila Carpentier, Christian Dina, et al.. Genomewide Association Study of a Rapid Progression Cohort Identifies New Susceptibility Alleles for AIDS (ANRS Genomewide Association Study 03). Journal of Infectious Diseases, 2009, 200 (8), pp.1194-1201. ⟨10.1086/605892⟩. ⟨hal-02566721⟩
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