Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population

Authors

• Andrey Shevchenko, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO); Saint Petersburg State University
• Daria V. Zhernakova, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO); University of Groningen - The Netherlands
• Sergey Malov, St. Petersburg State University - Russia; St. Petersburg Electrotechnical University - Russia
• Aleksey Komissarov, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO)
• Sofia Kolchanova, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO); Jetbrains Research
• Gaik Tamazian, St. Petersburg State University - Russia
• Alexey Antonik, St. Petersburg State University - Russia
• Nikolay Cherkasov, St. Petersburg State University - Russia
• Sergey Kliver, Siberian Branch of the Russian Academy of Sciences
• Anastasiia Turenko, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO)
• Mikhail Rotkevich, St. Petersburg State University - Russia
• Igor Evsyukov, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO)
• David Vlahov, Yale University
• Prisca K. Thami, University of Cape Town; Botswana Harvard AIDS Institute Partnership
• Simani Gaseitsiwe, Harvard T.H. Chan School of Public Health AIDS Initiative; Botswana Harvard AIDS Institute Partnership
• Vladimir Novitsky, Brown University; Botswana-Harvard AIDS Institute Partnership
• Myron Essex, Botswana-Harvard AIDS Institute Partnership; Harvard T.H. Chan School of Public Health
• Stephen James O'Brien, Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO); Nova Southeastern UniversityFollow

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

Publication Date

11-23-2021

Keywords

AIDS, HIV-C, GWAS, Botswana, GWATCH

Abstract

Although there have been many studies of gene variant association with different stages of HIV/AIDS progression in United States and European cohorts, few gene-association studies have assessed genic determinants in sub-Saharan African populations, which have the highest density of HIV infections worldwide. We carried out genome-wide association studies on 766 study participants at risk for HIV-1 subtype C (HIV-1C) infection in Botswana. Three gene associations (AP3B1, PTPRA, and NEO1) were shown to have significant association with HIV-1C acquisition. Each gene association was replicated within Botswana or in the United States–African American or United States–European American AIDS cohorts or in both. Each associated gene has a prior reported influence on HIV/AIDS pathogenesis. Thirteen previously discovered AIDS restriction genes were further replicated in the Botswana cohorts, extending our confidence in these prior AIDS restriction gene reports. This work presents an early step toward the identification of genetic variants associated with and affecting HIV acquisition or AIDS progression in the understudied HIV-1C afflicted Botswana population.

DOI

10.1073/pnas.2107830118

Volume

118

Issue

47

First Page

e2107830118

Comments

Significance

The search for genetic variants associated with resistance or susceptibility to HIV/AIDS already yielded insights that allowed developing therapeutics that contribute to dramatic reduction in AIDS-related comorbidities. Unfortunately, nearly all studies focused on European-descent populations, even though most infections happen in Africa. In this genome-wide association study we explored the genetic background of several hundred individuals from Botswana in search of associations with HIV infection. We discovered several genetic variant associations in genes implicated in HIV/AIDS pathogenesis. We also confirmed several associations reported in previous research. This study provides valuable data on the influence of human genetic variation on HIV-1C infection and pathogenesis in southern Africa, a region with the world’s largest number of HIV-1 infections.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2107830118/-/DCSupplemental.

Data Availability

SNP genotype data have been deposited in https://botswana.gen-watch.org/ (Botswana GWATCH database database). All other study data are included in the article and supporting information. Previously published data were used for this work (18).

Published under the PNAS license.

NSUWorks Citation

Shevchenko, Andrey; Daria V. Zhernakova; Sergey Malov; Aleksey Komissarov; Sofia Kolchanova; Gaik Tamazian; Alexey Antonik; Nikolay Cherkasov; Sergey Kliver; Anastasiia Turenko; Mikhail Rotkevich; Igor Evsyukov; David Vlahov; Prisca K. Thami; Simani Gaseitsiwe; Vladimir Novitsky; Myron Essex; and Stephen James O'Brien. 2021. "Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population." Proceedings of the National Academy of Sciences of the United States of America 118, (47): e2107830118. doi:10.1073/pnas.2107830118.