NIAID Ctr HIV AIDS VaccineLane, J.Mclaren, P. J.Dorrell, L.Shianna, K. V.Stemke, A.Pelak, K.Moore, S.Oldenburg, J.Alvarez-Roman, M. T.Angelillo-Scherrer, A.Boehlen, F.Bolton-Maggs, P. H. B.Brand, B.Brown, D.Chiang, E.Cid-Haro, A. R.Clotet, B.Collins, P.Colombo, S.Dalmau, J.Fogarty, P.Giangrande, P.Gringeri, A.Iyer, R.Katsarou, O.Kempton, C.Kuriakose, P.Lin, J.Makris, M.Manco-Johnson, M.Tsakiris, D. A.Martinez-Picado, J.Mauser-Bunschoten, E.Neff, A.Oka, S.Oyesiku, L.Parra, R.Peter-Salonen, K.Powell, J.Recht, M.Shapiro, A.Stine, K.Talks, K.Telenti, A.Wilde, J.Yee, T. T.Wolinsky, S. M.Martinson, J.Hussain, S. K.Bream, J. H.Jacobson, L. P.Carrington, M.Goedert, J. J.Haynes, B. F.Mcmichael, A. J.Goldstein, D. B.Fellay, J.2013-08-132013-08-132013-08-13201310.1093/hmg/ddt033https://infoscience.epfl.ch/handle/20.500.14299/94092WOS:000317431100019Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 D32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4) were homozygous for CCR5 32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.text::journal::journal article::research article