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Common genetic variation and the control of HIV-1 in humans

Fellay, J and Ge, D and Shianna, KV and Colombo, S and Ledergerber, B and Cirulli, ET and Urban, TJ and Zhang, K and Gumbs, CE and Smith, JP and Castagna, A and Cozzi-Lepri, A and De Luca, A and Easterbrook, P and Günthard, HF and Mallal, S and Mussini, C and Dalmau, J and Martinez-Picado, J and Miro, JM and Obel, N and Wolinsky, SM and Martinson, JJ and Detels, R and Margolick, JB and Jacobson, LP and Descombes, P and Antonarakis, SE and Beckmann, JS and O'Brien, SJ and Letvin, NL and McMichael, AJ and Haynes, BF and Carrington, M and Feng, S and Telenti, A and Goldstein, DB (2009) Common genetic variation and the control of HIV-1 in humans. PLoS Genetics, 5 (12). ISSN 1553-7390

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Abstract

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Fellay, J
Ge, D
Shianna, KV
Colombo, S
Ledergerber, B
Cirulli, ET
Urban, TJ
Zhang, K
Gumbs, CE
Smith, JP
Castagna, A
Cozzi-Lepri, A
De Luca, A
Easterbrook, P
Günthard, HF
Mallal, S
Mussini, C
Dalmau, J
Martinez-Picado, J
Miro, JM
Obel, N
Wolinsky, SM
Martinson, JJjmartins@pitt.eduJMARTINS
Detels, R
Margolick, JB
Jacobson, LP
Descombes, P
Antonarakis, SE
Beckmann, JS
O'Brien, SJ
Letvin, NL
McMichael, AJ
Haynes, BF
Carrington, M
Feng, S
Telenti, A
Goldstein, DB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMcCarthy, Mark I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 December 2009
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 5
Number: 12
DOI or Unique Handle: 10.1371/journal.pgen.1000791
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Adult; Alleles; Disease Progression; Female; Genetic Variation; Genotype; HIV Infections--virology; HIV-1--physiology; Humans; Kaplan-Meier Estimate; Major Histocompatibility Complex--genetics; Male; Phenotype; Polymorphism, Single Nucleotide--genetics; Viral Load
Other ID: NLM PMC2791220
PubMed Central ID: PMC2791220
PubMed ID: 20041166
Date Deposited: 03 Aug 2012 16:38
Last Modified: 02 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13304

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