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

McLaren, PJ; Pulit, SL; Gurdasani, D; Bartha, I; Shea, PR; Pomilla, C; Gupta, N; ... Fellay, J; + view all (2017) Evaluating the Impact of Functional Genetic Variation on HIV-1 Control. The Journal of Infectious Diseases , 216 (9) pp. 1063-1069. 10.1093/infdis/jix470. Green open access

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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

Type: Article
Title: Evaluating the Impact of Functional Genetic Variation on HIV-1 Control
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/infdis/jix470
Language: English
Additional information: © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Infectious Diseases, Microbiology, HIV-1 control, exome sequencing, HIV-1 progression, host genetics of infection, HIV host dependency factors, AUTISM SPECTRUM DISORDERS, WHOLE-GENOME ASSOCIATION, WIDE ASSOCIATION, RARE VARIANTS, HOST CONTROL, INFECTION, DETERMINANTS, POPULATION, LINKAGE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
URI: https://discovery.ucl.ac.uk/id/eprint/10043339
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