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

McLaren, P. J., Coulonges, C., Bartha, I., Lenz, T. L., Deutsch, A. J., Bashirova, A., et al. (2015). Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. Proceedings of the National Academy of Sciences of the United States of America. doi:10.1073/pnas.1514867112.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-1A6F-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-AFDF-D
Genre: Journal Article

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 Creators:
McLaren, Paul J., Author
Coulonges, Cedric, Author
Bartha, István, Author
Lenz, Tobias L.1, Author              
Deutsch, Aaron J., Author
Bashirova, Arman, Author
Buchbinder, Susan, Author
Carrington, Mary N., Author
Cossarizza, Andrea, Author
Dalmau, Judith, Author
Luca, Andrea De, Author
Goedert, James J., Author
Gurdasani, Deepti, Author
Haas, David W., Author
Herbeck, Joshua T., Author
Johnson, Eric O., Author
Kirk, Gregory D., Author
Lambotte, Olivier, Author
Luo, Ma, Author
Mallal, Simon, Author
van Manen, Daniélle, AuthorMartinez-Picado, Javier, AuthorMeyer, Laurence, AuthorMiro, José M., AuthorMullins, James I., AuthorObel, Niels, AuthorPoli, Guido, AuthorSandhu, Manjinder S., AuthorSchuitemaker, Hanneke, AuthorShea, Patrick R., AuthorTheodorou, Ioannis, AuthorWalker, Bruce D., AuthorWeintrob, Amy C., AuthorWinkler, Cheryl A., AuthorWolinsky, Steven M., AuthorRaychaudhuri, Soumya, AuthorGoldstein, David B., AuthorTelenti, Amalio, Authorde Bakker, Paul I. W., AuthorZagury, Jean-François, AuthorFellay, Jacques, Author more..
Affiliations:
1Emmy Noether Research Group Evolutionary Immunogenomics, Department Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2068286              

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Free keywords: HIV-1 control; GWAS; heritability; infectious disease; genomics
 Abstract: Previous genome-wide associat ion 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 Eur opean ancestry. The strongest sig- nal 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 a nalysis showed that this signal could not be fully attributed to the known protective CCR5 Δ 32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human ge- netic 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.

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Language(s): eng - English
 Dates: 2015-07-282015-10-132015-11-09
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1073/pnas.1514867112
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. USA
Source Genre: Journal
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Publ. Info: Washington, DC : National Academy of Sciences
Pages: 6 S. Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: /journals/resource/954925427230