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

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.

Automated summary

This study conducted genome-wide association studies on individuals at risk for HIV-1C infection in Botswana and identified three genes (AP3B1, PTPRA, and NEO1) significantly associated with HIV-1C acquisition. These gene associations were validated in Botswana, United States African American, and United States European American AIDS cohorts. Thirteen previously discovered AIDS restriction genes were also replicated in the Botswana cohorts, contributing to the understanding of genetic variants affecting HIV acquisition and AIDS progression in the understudied HIV-1C population in Botswana.