biostudies-literatureMcLaren PJNIDA NIH HHSHoward Hughes Medical InstituteNIAID NIH HHS14658-63https://www.ebi.ac.uk/biostudies/studies/S-EPMC4664299biostudies-literatureUnknown112(47)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 signProceedings of the National Academy of Sciences of the United States of AmericaPolymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.PMC4664299P01 AI057005U01 DA036297K24 AI118591R01 DA012568R01 AI077505Walker BDWolinsky SMvan Manen DGoldstein DBMcLaren PJHerbeck JTZagury JFRaychaudhuri SCossarizza ATheodorou IPoli GSchuitemaker HFellay JMullins JIde Bakker PIHaas DWDe Luca AMartinez-Picado JGoedert JJBartha IWinkler CAShea PRCarrington MNCoulonges CLenz TLMeyer LObel NMiro JMLambotte ODeutsch AJKirk GDBashirova AMallal STelenti ALuo MSandhu MSWeintrob ACBuchbinder SDalmau JJohnson EOGurdasani DfalsePolymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.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 sign2015-01-01T00:00:00Z2015 Nov2026-05-05T07:53:40.331Z2019-03-27T02:02:58ZS-EPMC46642992655397410.1073/pnas.1514867112