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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure
PLoS ONE, Volume 6, No. 12, Article e28632, Year 2011
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Description
Background: Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. Methods: We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. Results: After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. Conclusion: This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition. © 2011 Lingappa et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3236203/bin/pone.0028632.s001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3236203/bin/pone.0028632.s002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3236203/bin/pone.0028632.s003.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3236203/bin/pone.0028632.s004.doc
Authors & Co-Authors
Lingappa, Jairam R.
United States, Seattle
University of Washington
Petrovski, Slavé D.Sign©
United States, Durham
Duke University
Australia, Melbourne
University of Melbourne
Kahle, Erin M.
United States, Seattle
University of Washington
Fellay, Jacques
United States, Durham
Duke University
Shianna, Kevin V.
United States, Durham
Duke University
McElrath, Margaret Juliana
United States, Seattle
Fred Hutchinson Cancer Research Center
Thomas, Katherine K.
United States, Seattle
University of Washington
Baeten, Jared M.
United States, Seattle
University of Washington
Celum, Connie L.
United States, Seattle
University of Washington
Wald, Anna
United States, Seattle
University of Washington
United States, Seattle
Fred Hutchinson Cancer Research Center
De Bruyn, Guy
South Africa, Johannesburg
University of the Witwatersrand
Mullins, James I.
United States, Seattle
University of Washington
Nakku-Joloba, Edith
Uganda, Kampala
Makerere University
Farquhar, Carey
United States, Seattle
University of Washington
Essex, Max E.
United States, Cambridge
Harvard University
Donnell, Deborah J.
United States, Seattle
Fred Hutchinson Cancer Research Center
Kiarie, James Njogu
Kenya, Nairobi
University of Nairobi
Haynes, Barton F.
United States, Durham
Duke University
Goldstein, David B.
United States, Durham
Duke University
Statistics
Citations: 77
Authors: 19
Affiliations: 8
Identifiers
Doi:
10.1371/journal.pone.0028632
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cohort Study
Study Approach
Quantitative