title: Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America. lingappa@UW.edu
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.forename: Slavé
authors.initials: S
authors.lastname: Petrovski
authors.forename: Erin
authors.initials: E
authors.lastname: Kahle
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Kevin
authors.initials: K
authors.lastname: Shianna
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Thomas
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Edith
authors.initials: E
authors.lastname: Nakku-Joloba
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Bart
authors.initials: B
authors.lastname: Haynes
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern / Q000453:epidemiology; D000368:Aged; D005191:Family Characteristics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000635:transmission / Q000821:virology*; D006679:HIV Seropositivity / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult