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Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236203/ https://www.ncbi.nlm.nih.gov/pubmed/22174851 http://dx.doi.org/10.1371/journal.pone.0028632 |
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author | Lingappa, Jairam R. Petrovski, Slavé Kahle, Erin Fellay, Jacques Shianna, Kevin McElrath, M. Juliana Thomas, Katherine K. Baeten, Jared M. Celum, Connie Wald, Anna de Bruyn, Guy Mullins, James I. Nakku-Joloba, Edith Farquhar, Carey Essex, Max Donnell, Deborah Kiarie, James Haynes, Bart Goldstein, David |
author_facet | Lingappa, Jairam R. Petrovski, Slavé Kahle, Erin Fellay, Jacques Shianna, Kevin McElrath, M. Juliana Thomas, Katherine K. Baeten, Jared M. Celum, Connie Wald, Anna de Bruyn, Guy Mullins, James I. Nakku-Joloba, Edith Farquhar, Carey Essex, Max Donnell, Deborah Kiarie, James Haynes, Bart Goldstein, David |
author_sort | Lingappa, Jairam R. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3236203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32362032011-12-15 Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure Lingappa, Jairam R. Petrovski, Slavé Kahle, Erin Fellay, Jacques Shianna, Kevin McElrath, M. Juliana Thomas, Katherine K. Baeten, Jared M. Celum, Connie Wald, Anna de Bruyn, Guy Mullins, James I. Nakku-Joloba, Edith Farquhar, Carey Essex, Max Donnell, Deborah Kiarie, James Haynes, Bart Goldstein, David PLoS One Research Article 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. Public Library of Science 2011-12-12 /pmc/articles/PMC3236203/ /pubmed/22174851 http://dx.doi.org/10.1371/journal.pone.0028632 Text en Lingappa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lingappa, Jairam R. Petrovski, Slavé Kahle, Erin Fellay, Jacques Shianna, Kevin McElrath, M. Juliana Thomas, Katherine K. Baeten, Jared M. Celum, Connie Wald, Anna de Bruyn, Guy Mullins, James I. Nakku-Joloba, Edith Farquhar, Carey Essex, Max Donnell, Deborah Kiarie, James Haynes, Bart Goldstein, David Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title | Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title_full | Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title_fullStr | Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title_full_unstemmed | Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title_short | Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure |
title_sort | genomewide association study for determinants of hiv-1 acquisition and viral set point in hiv-1 serodiscordant couples with quantified virus exposure |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236203/ https://www.ncbi.nlm.nih.gov/pubmed/22174851 http://dx.doi.org/10.1371/journal.pone.0028632 |
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