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Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study

Author

Listed:
  • Eric O Johnson
  • Dana B Hancock
  • Nathan C Gaddis
  • Joshua L Levy
  • Grier Page
  • Scott P Novak
  • Cristie Glasheen
  • Nancy L Saccone
  • John P Rice
  • Michael P Moreau
  • Kimberly F Doheny
  • Jane M Romm
  • Andrew I Brooks
  • Bradley E Aouizerat
  • Laura J Bierut
  • Alex H Kral

Abstract

Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV- controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women’s Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10-4), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10-7 vs. P

Suggested Citation

  • Eric O Johnson & Dana B Hancock & Nathan C Gaddis & Joshua L Levy & Grier Page & Scott P Novak & Cristie Glasheen & Nancy L Saccone & John P Rice & Michael P Moreau & Kimberly F Doheny & Jane M Romm &, 2015. "Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-15, March.
    • Handle: RePEc:plo:pone00:0118149
    DOI: 10.1371/journal.pone.0118149
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    1. Stephen B. Montgomery & Micha Sammeth & Maria Gutierrez-Arcelus & Radoslaw P. Lach & Catherine Ingle & James Nisbett & Roderic Guigo & Emmanouil T. Dermitzakis, 2010. "Transcriptome genetics using second generation sequencing in a Caucasian population," Nature, Nature, vol. 464(7289), pages 773-777, April.
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