The Collaborative African Genomics Network (CAfGEN): Applying Genomic technologies to probe host factors important to the progression of HIV and HIV-tuberculosis infection in sub-Saharan Africa

Abstract

Background: The Human Heredity and Health in Africa consortium (H3Africa) was conceived to facilitate the application of genomics technologies to improve health across Africa. Here, we describe how the Collaborative African Genomics Network (CAfGEN) of the H3Africa consortium is using genomics to probe host genetic factors important to the progression of HIV and HIV-tuberculosis (TB) coinfection in sub-Saharan Africa. Methods: CAfGEN is an H3Africa collaborative centre comprising expertise from the University of Botswana; Makerere University; Baylor College of Medicine Children’s Clinical Centers of Excellence (COEs) in Botswana, Uganda, and Swaziland; as well as Baylor College of Medicine, Texas. The COEs provide clinical expertise for community engagement, participant recruitment and sample collection while the three University settings facilitate processing and management of genomic samples and provide infrastructure and training opportunities to sustain genomics research. Results: The project has focused on utilizing whole-exome sequencing to identify genetic variants contributing to extreme HIV disease progression phenotypes in children, as well as RNA sequencing and integrated genomics to identify host genetic factors associated with TB disease progression among HIV-positive children. These cohorts, developed using the COEs’ electronic medical records, are exceptionally well-phenotyped and present an unprecedented opportunity to assess genetic factors in individuals whose HIV was acquired by a different route than their adult counterparts in the context of a unique clinical course and disease pathophysiology. Conclusions: Our approach offers the prospect of developing a critical mass of well-trained, highly-skilled, continent-based African genomic scientists. To ensure long term genomics research sustainability in Africa, CAfGEN contributes to a wide range of genomics capacity and infrastructure development on the continent, has laid a foundation for genomics graduate programs at its institutions, and continues to actively promote genomics research through innovative forms of community engagement brokered by partnerships with governments and academia to support genomics policy formulation.

The epidemiology of psychiatric disorders in Africa: a scoping review

“…Furthermore, strengthening the infrastructure and capacity for conducting psychiatric epidemiologic research in Africa will facilitate further understanding of the role of genetic and environmental factors while also building equitable partnerships and ownership of psychiatric genetic epidemiology research among scientists in Africa. There is a rich history of genetics and epidemiologic research on HIV/AIDS, 104,105 malaria, 106 chronic and infectious diseases 107 in Africa, including one of the first large-scale genomic studies of HIV and tuberculosis coinfection, 108 which have significantly advanced the global knowledge of the etiology of these diseases. Future research should now include efforts to understand and measure culture-bound syndromes, unique presentations of and measurement considerations for DSM and ICD psychiatric disorders, and relevant disorders that were not covered in this review (e.g., autism spectrum disorder, epilepsy).…”

Do solidarity and reciprocity obligations compel African researchers to feedback individual genetic results in genomics research?

“…As a result of this HIV/TB burden, the Collaborative African Genomics Network (CAfGEN) conducted at BBCCCE, was initiated to study genes of children with HIV and TB, to inform the development of new therapies to prevent or supress these infections [ 32 ]. The CAfGEN study is a collaborative project within the Human Heredity and Health for Africa (H3Africa) Consortium [ 33 ] and uses genomics approaches to identify host genetic factors that are important for the progression of HIV and HIV-TB infection in paediatric and adolescent African populations [ 34 ]. This genomic study was selected as a case study because it is amongst the few genomic studies being conducted in Botswana and offered an opportunity to explore questions around the feedback of individual results in a genomics research.…”

Considerations of Autonomy in Guiding Decisions around the Feedback of Individual Genetic Research Results from Genomics Research: Expectations of and Preferences from Researchers in Botswana

“…The study was part of a multicountry qualitative study conducted in three African countries: Botswana, South Africa, and Cameroon, under the auspices of the H3Africa Consortium but only results from Botswana are presented. The study was hosted by the Collaborative African Genomics Network (CAfGEN) coordinated at Botswana-Baylor Children's Clinical Center of Excellence which looked at a subset of HIV-positive children in Botswana to find out the host genetic factors that influence disease progression among pediatric Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) infections that may account for some of the variability in the progression of this disease [ 18 ]. This study provided an anchor for our study as it has the potential of generating clinically important genetic results.…”