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Published on: August 31, 2014
Evaluating the Impact of Functional Genetic Variation on HIV-1 Control
Paul J McLaren1,2, Sara L Pulit3, Deepti Gurdasani4,5
1JC Wilt Infectious Diseases Research Centre, National HIV and Retrovirology Laboratory, Public Health Agency of Canada.
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.
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