H3Africa is developing capacity for health-related genomics research in Africa

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.

There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent.