DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Setpoint viral load in HIV-1 infection. The EFO term HIV-1 infection, HIV viral set point measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: HIV-1 infection, HIV viral set point measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

PJ McLaren, C Coulonges, I Bartha, TL Lenz, AJ Deutsch, A Bashirova, S Buchbinder, MN Carrington, A Cossarizza, J Dalmau, A De Luca, JJ Goedert, D Gurdasani, DW Haas, JT Herbeck, EO Johnson, GD Kirk, O Lambotte, M Luo, S Mallal, D van Manen, J Martinez-Picado, L Meyer, JM Miro, JI Mullins, N Obel, G Poli, MS Sandhu, H Schuitemaker, PR Shea, I Theodorou, BD Walker, AC Weintrob, CA Winkler, SM Wolinsky, S Raychaudhuri, DB Goldstein, A Telenti, PI de Bakker, JF Zagury, J Fellay

TITLE:

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

JOURNAL:

Proceedings of the National Academy of Sciences of the United States of America Nov 2015, Vol 112, pp. 14658-63

ABSTRACT:

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward. PUBMED: 26553974
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