title: Common genetic variation and the control of HIV-1 in humans.
abstract: To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.
authors.affiliation: Center for Human Genome Variation, Duke Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Sara
authors.initials: S
authors.lastname: Colombo
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Cirulli
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Urban
authors.forename: Kunlin
authors.initials: K
authors.lastname: Zhang
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Gumbs
authors.forename: Jason P
authors.initials: JP
authors.lastname: Smith
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Judith
authors.initials: J
authors.lastname: Dalmau
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: José M
authors.initials: JM
authors.lastname: Miro
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Martinson
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
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: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Sheng
authors.initials: S
authors.lastname: Feng
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019562:Viral Load