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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.

Publication ,  Journal Article
Lingappa, JR; Petrovski, S; Kahle, E; Fellay, J; Shianna, K; McElrath, MJ; Thomas, KK; Baeten, JM; Celum, C; Wald, A; de Bruyn, G; Mullins, JI ...
Published in: PLoS One
2011

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28632

Location

United States

Related Subject Headings

  • Young Adult
  • Middle Aged
  • Male
  • Humans
  • HIV-1
  • HIV Seropositivity
  • HIV Infections
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

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Lingappa, J. R., Petrovski, S., Kahle, E., Fellay, J., Shianna, K., McElrath, M. J., … Partners in Prevention HSV/HIV Transmission Study Team, . (2011). Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One, 6(12), e28632. https://doi.org/10.1371/journal.pone.0028632
Lingappa, Jairam R., Slavé Petrovski, Erin Kahle, Jacques Fellay, Kevin Shianna, M Juliana McElrath, Katherine K. Thomas, et al. “Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.PLoS One 6, no. 12 (2011): e28632. https://doi.org/10.1371/journal.pone.0028632.
Lingappa JR, Petrovski S, Kahle E, Fellay J, Shianna K, McElrath MJ, et al. Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One. 2011;6(12):e28632.
Lingappa, Jairam R., et al. “Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.PLoS One, vol. 6, no. 12, 2011, p. e28632. Pubmed, doi:10.1371/journal.pone.0028632.
Lingappa JR, Petrovski S, Kahle E, Fellay J, Shianna K, McElrath MJ, Thomas KK, Baeten JM, Celum C, Wald A, de Bruyn G, Mullins JI, Nakku-Joloba E, Farquhar C, Essex M, Donnell D, Kiarie J, Haynes B, Goldstein D, Partners in Prevention HSV/HIV Transmission Study Team. Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One. 2011;6(12):e28632.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28632

Location

United States

Related Subject Headings

  • Young Adult
  • Middle Aged
  • Male
  • Humans
  • HIV-1
  • HIV Seropositivity
  • HIV Infections
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation