A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Lane, J; McLaren, P; Dorrell, L; Shianna, K; Stemke, A; Pelak, K; Moore, S; Oldenburg, J; Alvarez-Roman, M; Angelillo-Scherrer, A; Boehlen, F; Bolton-Maggs, P; Brand, B; Brown, D; Chiang, E; Cid-Haro, A; Clotet, B; Collins, P; Colombo, S; Dalmau, J; Fogarty, P; Giangrande, P; Gringeri, A; Iyer, R; Katsarou, O

Journal article

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Abstract:: Human 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 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 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.

Publication status:: Published

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APA Style

Lane, J., McLaren, P., Dorrell, L., Shianna, K., Stemke, A., Pelak, K., Moore, S., Oldenburg, J., Alvarez-Roman, M., Angelillo-Scherrer, A., Boehlen, F., Bolton-Maggs, P., Brand, B., Brown, D., Chiang, E., Cid-Haro, A., Clotet, B., Collins, P., Colombo, S., … Katsarou, O. (2013). A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Human Molecular Genetics, 22(9), 1903–1910.

MLA Style

Lane, J., et al. “A Genome-Wide Association Study of Resistance to HIV Infection in Highly Exposed Uninfected Individuals with Hemophilia A.” Human Molecular Genetics, vol. 22, no. 9, 2013, pp. 1903–10.

Chicago Style

Lane, J, P McLaren, L Dorrell, K Shianna, A Stemke, K Pelak, S Moore, et al. 2013. “A Genome-Wide Association Study of Resistance to HIV Infection in Highly Exposed Uninfected Individuals with Hemophilia A.” Human Molecular Genetics 22 (9): 1903–10.
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