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PLoS Pathog DOI:10.1371/journal.ppat.1003515

Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.

Publication TypeJournal Article
Year of Publication2013
AuthorsMcLaren, PJ, Coulonges, C, Ripke, S, van den Berg, L, Buchbinder, S, Carrington, M, Cossarizza, A, Dalmau, J, Deeks, SG, Delaneau, O, De Luca, A, Goedert, JJ, Haas, D, Herbeck, JT, Kathiresan, S, Kirk, GD, Lambotte, O, Luo, M, Mallal, S, van Manen, D, Martinez-Picado, J, Meyer, L, Miro, JM, Mullins, JI, Obel, N, O'Brien, SJ, Pereyra, F, Plummer, FA, Poli, G, Qi, Y, Rucart, P, Sandhu, MS, Shea, PR, Schuitemaker, H, Theodorou, I, Vannberg, F, Veldink, J, Walker, BD, Weintrob, A, Winkler, CA, Wolinsky, S, Telenti, A, Goldstein, DB, de Bakker, PIW, Zagury, J-F, Fellay, J
JournalPLoS Pathog
Volume9
Issue7
Pagese1003515
Date Published2013
ISSN1553-7374
KeywordsCase-Control Studies, Cohort Studies, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Polymorphism, Single Nucleotide
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 of CCR5Δ32 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.

URLhttp://dx.plos.org/10.1371/journal.ppat.1003515
DOI10.1371/journal.ppat.1003515
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23935489?dopt=Abstract

Alternate JournalPLoS Pathog.
PubMed ID23935489
PubMed Central IDPMC3723635
Grant ListU01 DA036297 / DA / NIDA NIH HHS / United States
R01 HL087676 / HL / NHLBI NIH HHS / United States
HHSN26120080001E / / PHS HHS / United States
T32 AI007140 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States
R37 AI047734 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 DA012568 / DA / NIDA NIH HHS / United States