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Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.

Published version
Peer-reviewed

Type

Article

Change log

Authors

McLaren, Paul J 
Pulit, Sara L 
Gurdasani, Deepti 
Bartha, Istvan 
Shea, Patrick R 

Abstract

Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results: Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions: These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.

Description

Keywords

HIV host dependency factors, HIV-1 control, HIV-1 progression, exome sequencing, host genetics of infection, Adult, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Viral Load, Whole Exome Sequencing

Journal Title

Journal of Infectious Diseases

Conference Name

Journal ISSN

1537-6613
1537-6613

Volume Title

216

Publisher

Oxford University Press
Sponsorship
Medical Research Council (G0901213)
Medical Research Council (MR/K013491/1)
Medical Research Council (G0701652)