title: Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.
abstract: OBJECTIVE
  To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. We investigated whether common genetic variants associate with HIV-1 susceptibility in Africans.
  
  
  METHODS
  We performed a genome-wide association study (GWAS) in a population of 1532 individuals from Malawi, a country with high prevalence of HIV-1 infection. Using single-nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing.
  
  
  RESULTS
  After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk 2.0 or more and minor allele frequencies 12% or more.
  
  
  CONCLUSIONS
  This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to nongenetic parameters or to complex interactions between genes, immunity and environment.
authors.affiliation: Center for Human Genome Variation, School of Medicine, Duke University, Durham, North Carolina 27708, USA. slave.petrovski@duke.edu
authors.forename: Slavé
authors.initials: S
authors.lastname: Petrovski
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Nicole
authors.initials: N
authors.lastname: Carpenetti
authors.forename: Johnstone
authors.initials: J
authors.lastname: Kumwenda
authors.forename: Gift
authors.initials: G
authors.lastname: Kamanga
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Kamwendo
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000235:genetics*; D055815:Young Adult
chemical_list: D019713:Receptors, CCR5