Biology Faculty Articles
Document Type
Article
Publication Date
7-25-2013
Publication Title
PLoS Pathogens
ISSN
1553-7366
Volume
9
Issue/No.
7 e1003515
First Page
1
Last Page
9
Abstract
Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception ofCCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.
Additional Comments
National Cancer Institute contract #: HHSN26120080001E; National Heart, Lung, and Blood Institute grant #: R01 HL087676
NSUWorks Citation
McLaren, Paul J.; Cedric Coulonges; Stephan Ripke; Leonard H. van den Berg; Susan Buchbinder; Mary Carrington; Andrea Cossarizza; Judith Dalmau; Steven G. Deeks; Olivier Delaneau; Andrea De Luca; James J. Goedert; David W. Haas; Joshua T. Herbeck; Sekar Kathiresan; Gregory D. Kirk; Olivier Lambotte; Ma Luo; Simon Mallal; Danielle van Manen; Javier Martinez-Picado; Florencia Pereyra; Francis A. Plummer; Guido Poli; Ying Qi; Pierre Rucart; Manj S. Sandhu; Patrick R. Shea; Hanneke Schuitemaker; Ioannis Theodorou; Fredrik Vannberg; Jan Veldink; Bruce D. Walker; Amy C. Weintrob; Cheryl Winkler; Steven M. Wolinsky; Amalio Telenti; David B. Goldstein; Paul I. W. de Bakker; Jean-Francois Zagury; and Jacques Fellay. 2013. "Association Study of Common Genetic Variants and HIV- 1 Acquisition in 6,300 Infected Cases and 7,200 Controls." PLoS Pathogens 9, (7 e1003515): 1-9. https://nsuworks.nova.edu/cnso_bio_facarticles/742
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Included in
Genetics and Genomics Commons, Immunology and Infectious Disease Commons, Medicine and Health Sciences Commons
Comments
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.