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

Jérôme Lane, Paul J McLaren, Lucy Dorrell, Kevin V Shianna, Amanda Stemke, Kimberly Pelak, Stephen Moore, Johannes Oldenburg, Maria Teresa Alvarez-Roman, Anne Angelillo-Scherrer, Francoise Boehlen, Paula H B Bolton-Maggs, Brigit Brand, Deborah Brown, Elaine Chiang, Ana Rosa Cid-Haro, Bonaventura Clotet, Peter Collins, Sara Colombo, Judith DalmauPatrick Fogarty, Paul Giangrande, Alessandro Gringeri, Rathi Iyer, Olga Katsarou, Christine Kempton, Philip Kuriakose, Judith Lin, Mike Makris, Marilyn Manco-Johnson, Dimitrios A Tsakiris, Javier Martinez-Picado, Evelien Mauser-Bunschoten, Anne Neff, Shinichi Oka, Lara Oyesiku, Rafael Parra, Kristiina Peter-Salonen, Jerry Powell, Michael Recht, Amy Shapiro, Kimo Stine, Katherine Talks, Amalio Telenti, Jonathan Wilde, Thynn Thynn Yee, Steven M Wolinsky, Jeremy Martinson, Shehnaz K Hussain, Jay H Bream,

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1903-1910
Number of pages8
JournalHuman Molecular Genetics
Issue number9
Publication statusPublished - 2013


  • Adult
  • DNA Copy Number Variations
  • Disease Resistance
  • Epistasis, Genetic
  • Factor VIII
  • Female
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • HIV Infections
  • HIV Seropositivity
  • Hemophilia A
  • Heterozygote
  • Homozygote
  • Humans
  • Logistic Models
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Receptors, CCR5


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