Genomic studies have become one of the potential tools that could aid in the understanding disease. HIV disease progression and active TB infection have been studied using these genomic methods to interrogate host factors associated with these diseases and their progression. Prior work has focused on adult populations and limited African cohorts. The Collaborative African Genomics Network aims to fill this gap by conducting HIV and TB disease mapping studies in African children to understand how genetic variation impacts disease progression through the use of genomic technologies. A cohort of 1000 well-phenotyped paediatric perinatally HIV-infected patients has been recruited at 2 Baylor International Paediatric AIDS Initiative Centres of Excellence in Botswana and Uganda. 200 long-term non progressors (LTNP) - not needing antiretroviral treatment or asymptomatic for HIV disease 10 years after perinatal infection, and 200 rapid progressors (RP) samples â€“ having two or more CD4 T cell percentage values <15% within three years after birth, with no value >15% afterwards in the absence of ART; and/or ART initiated within three years after birth, and at least one preceding CD4<15%; and/or AIDS-defining illness (CDC category 3 or WHO stage 3/4), will be utilised in the discovery of novel and known variants associated with HIV disease progression. Candidate variants from the discovery phase will be replicated with the other 300 LTNP/RP samples.
The Schizophrenia in the African Xhosa Population (SAX) study aims to determine the underlying genetic causes of schizophrenia in the Xhosa population, through whole exome sequencing, and genome wide association studies. A total of 1400 Xhosa individuals with schizophrenia, and 1400 age- and sex-matched Xhosa unaffected controls, will be recruited from regions in the Western and Eastern Cape in South Africa. Isolated DNA will undergo whole exome sequencing at Baylor College, USA. In addition, a subset of samples (N=400) will be selected for analysis on the Cytoscan HD Array (Affymetrix), a platform that enables the detection of whole genome copy number variation. Thereafter, the study aims to screen all cases and controls on an African-specific, copy number dense chip.
Stroke, a leading cause of death and disability in Africans, is the clinical culmination of several complex and interacting biological processes, precipitated by various genetic and environmental factors. SIREN aims to comprehensively investigate the socio-demographic, clinical and genetic characteristics of stroke among Black stroke patients in Africa, and compare and validate findings with a cohort of African American stroke survivors (REGARDS cohort), 80% of whom migrated from West Africa (SIREN recruitment sites). Simultaneously, we are building sustainable capacities in Phenomics, Biobanking, Genomics, Biostatistics and Bioinformatics for future high-level investigation of stroke and other vascular disease entities in Africa. With a central hypothesis that distribution of unique established and novel genomic and environmental factors will account for the peculiar and hitherto unreported pattern, incidence, type, subtype and outcome of stroke among individuals of African ancestry, we are employing a multi-pronged multi-stage strategy for the discovery and validation phases of our Genomics core. With proposed GWAS 3000 matched case-control pairs, we have 99.65% power to detect at least one causal SNP with Genetic Relative Risk (GRR) of 1.5 with allele frequency as low as 0.04 and 87.42% power to detect 20 causal variants. This will be followed up by additional discovery phases using other techniques followed by validation and functional genomics and transomics. We will also utilise our data to explore the genomic and environmental determinants of a broad range of cardiovascular risk factors.
The TrypanoGEN network is consortium of researchers from Burkina Faso, Cameroon, Coˆte d’Ivoire, Guinea, Democratic Republic of Congo (DRC), Malawi, Uganda, Zambia, France, the UK, and Belgium. The network is aimed at identifying the human genetic determinants of susceptibility/resistance to sleeping sickness in the different African endemic populations. For this, the TrypanoGEN project has created a biobank of specimens with standardized parasitological and clinical data (Ilboudo eta l., 2017); a resource, which will enable the first GWAS of Human African Trypanosomiasis using a large, and well-characterized specimen collection originating from different populations.