TY - JOUR
T1 - Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition
AU - Limou, Sophie
AU - Delaneau, Olivier
AU - Van Manen, Daniëlle
AU - An, Ping
AU - Sezgin, Efe
AU - Le Clerc, Sigrid
AU - Coulonges, Cédric
AU - Troyer, Jennifer L.
AU - Veldink, Jan H.
AU - Van Den Berg, Leonard H.
AU - Spadoni, Jean Louis
AU - Taing, Lieng
AU - Labib, Taoufik
AU - Montes, Matthieu
AU - Delfraissy, Jean François
AU - Schachter, François
AU - O'Brien, Stephen J.
AU - Buchbinder, Susan
AU - Van Natta, Mark L.
AU - Jabs, Douglas A.
AU - Froguel, Philippe
AU - Schuitemaker, Hanneke
AU - Winkler, Cheryl A.
AU - Zagury, Jean François
N1 - Funding Information:
This project has been funded in part by federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH) (contract HHSN26120080001E) and by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Funding Information:
The LSOCA is supported by cooperative agreements from the National Eye Institute, NIH, to The Mount Sinai School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067).
Funding Information:
The authors acknowledge funding from the Netherlands Organization for Scientific Research (TOP; registration number 9120.6046). The Amsterdam Cohort Studies on HIVI infection and AIDS, a collaboration between the Amsterdam Health Service, the Academic Medical Center of the University of Amsterdam, Sanquin Research, and the University Medical Center Utrecht, are part of the Netherlands HIV Monitoring Foundation and are financially supported by the Netherlands National Institute for Public Health and the Environment.
Funding Information:
Financial support. This work was supported by Agence Nationale de Recherche sur le SIDA: Sidaction: the Conservatoire National des Arts et Metiers: Neovacs SA: and Vaxconsulting.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10 -5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10 -8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.
AB - Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10 -5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10 -8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.
UR - http://www.scopus.com/inward/record.url?scp=84858272542&partnerID=8YFLogxK
U2 - 10.1093/infdis/jis028
DO - 10.1093/infdis/jis028
M3 - Article
C2 - 22362864
AN - SCOPUS:84858272542
SN - 0022-1899
VL - 205
SP - 1155
EP - 1162
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -