Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

Détails

ID Serval
serval:BIB_2A6736196FCC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
McLaren P.J., Coulonges C., Bartha I., Lenz T.L., Deutsch A.J., Bashirova A., Buchbinder S., Carrington M.N., Cossarizza A., Dalmau J., De Luca A., Goedert J.J., Gurdasani D., Haas D.W., Herbeck J.T., Johnson E.O., Kirk G.D., Lambotte O., Luo M., Mallal S., van Manen D., Martinez-Picado J., Meyer L., Miro J.M., Mullins J.I., Obel N., Poli G., Sandhu M.S., Schuitemaker H., Shea P.R., Theodorou I., Walker B.D., Weintrob A.C., Winkler C.A., Wolinsky S.M., Raychaudhuri S., Goldstein D.B., Telenti A., de Bakker P.I., Zagury J.F., Fellay J.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
24/11/2015
Peer-reviewed
Oui
Volume
112
Numéro
47
Pages
14658-14663
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.
Mots-clé
Adult, Alleles, Amino Acids/genetics, Chromosomes, Human, Pair 3/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, HIV-1/genetics, HLA-B Antigens/genetics, Host-Pathogen Interactions/genetics, Humans, Inheritance Patterns/genetics, Physical Chromosome Mapping, Polymorphism, Single Nucleotide/genetics, Receptors, CCR5/genetics, Viral Load/genetics, GWAS, HIV-1 control, genomics, heritability, infectious disease
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/10/2017 9:03
Dernière modification de la notice
09/10/2023 16:01
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