Common genetic variation and the control of HIV-1 in humans.
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.
Fellay
Jacques
J
Center for Human Genome Variation, Duke Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA.
Ge
Dongliang
D
Shianna
Kevin V
KV
Colombo
Sara
S
Ledergerber
Bruno
B
Cirulli
Elizabeth T
ET
Urban
Thomas J
TJ
Zhang
Kunlin
K
Gumbs
Curtis E
CE
Smith
Jason P
JP
Castagna
Antonella
A
Cozzi-Lepri
Alessandro
A
De Luca
Andrea
A
Easterbrook
Philippa
P
Günthard
Huldrych F
HF
Mallal
Simon
S
Mussini
Cristina
C
Dalmau
Judith
J
Martinez-Picado
Javier
J
Miro
José M
JM
Obel
Niels
N
Wolinsky
Steven M
SM
Martinson
Jeremy J
JJ
Detels
Roger
R
Margolick
Joseph B
JB
Jacobson
Lisa P
LP
Descombes
Patrick
P
Antonarakis
Stylianos E
SE
Beckmann
Jacques S
JS
O'Brien
Stephen J
SJ
Letvin
Norman L
NL
McMichael
Andrew J
AJ
Haynes
Barton F
BF
Carrington
Mary
M
Feng
Sheng
S
Telenti
Amalio
A
Goldstein
David B
DB
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