title: Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.
abstract: BACKGROUND
  AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (<2 years) and long-term non-progression (>15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS.
  
  
  METHODS
  The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints.
  
  
  RESULTS
  Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression.
  
  
  CONCLUSIONS
  Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Manen
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Brigitte D
authors.initials: BD
authors.lastname: Boeser-Nunnink
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.forename: Sebastiaan M
authors.initials: SM
authors.lastname: Bol
authors.forename: Judith A
authors.initials: JA
authors.lastname: Burger
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Perry D
authors.initials: PD
authors.lastname: Moerland
authors.forename: Ruben
authors.initials: R
authors.lastname: van 't Slot
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
authors.forename: Angélique B
authors.initials: AB
authors.lastname: van 't Wout
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000235:genetics* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016019:Survival Analysis; D019562:Viral Load / Q000235:genetics; D055815:Young Adult