Aims and Objectives
The long-term vision of the Collaborative Centre is to build capacity in Africa for research that leads to an understanding of and response to the interplay between genetic, epigenetic and environmental risk factors for obesity and associated cardiometabolic disease (CMD) in sub-Saharan Africa. The objective is to develop capability that enables the use of genomics in addressing questions of biomedical importance.
The Collaborative Center will be consolidated under the auspices of the University of the Witwatersrand (Wits) and the International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries (INDEPTH)(www.indepth-network.org). It will capitalize on the strengths of existing longitudinal cohorts, including the urban Soweto (Birth to Twenty cohort) and rural Agincourt research platforms in South Africa (Wits based), and the well-established INDEPTH health and demographic surveillance centers in Kenya, Ghana, Tanzania, Burkina Faso and South Africa. The centers offer established infrastructure, trained fieldworkers, long-standing community engagement and service links, and detailed longitudinal and phenotype data. Genetic, genomic and, at a later stage, epigenetic studies will be conducted on biological specimens already collected, and additional prospective sampling, with harmonized phenotyping across sites. Already, key genetic studies involving the Soweto Birth to Twenty cohort are underway.
The project will aim to collect 2000 DNA samples (equivalent numbers of males and females; aged 40-60 years), following informed consent, from each of six sites, two each in western (Ghana and Burkina Faso), eastern (Kenya and Tanzania) and southern Africa (South Africa), contrasting urban and rural communities risk of obesity and related metabolic disorders. The Collaborative Center will bring together a powerful team of researchers on the African continent.
The Collaborative Center will address three broad themes:
- Capacity development to enhance capability for genomic research in Africa to address critical problems of health and disease;
- Understanding the genomic architecture of sub-Saharan African populations and its impact on disease susceptibility; and
- To identify genetic, genomic and environmental risk factors for obesity by leveraging on existing longitudinal cohorts and adding a genomic dimension to the research.
- Specific aims will be addressed in this application under three collaborating components:
- Epidemiology, phenotyping and sampling;
- Genomic architecture of African populations; and
- Body composition and CMD risk.
Aim 1: To build sustainable capability for genomic and genetic research on the African continent.
This is the main objective of the H3Africa initiative and this proposal, and will be achieved through a collaborative research program that emphasizes training and skills development, including engagement with communities and services, as well as building basic laboratory infrastructure across five African countries.
(Theme A; collaborating components 1, 2 & 3)
Aim 2: To investigate and understand genome structure in sub-Saharan African populations in west, east and South Africa.
African populations are genetically diverse and harbor signatures of intercontinental admixture, immigration, responses to selection and random drift. We hypothesize that a better understanding of the way in which these factors influence susceptibility to disease will contribute to predicting future health on the continent, in the context of modified environmental factors.
(Themes A & B; Collaborating component 1)
Aim 3: To identify genetic variants that influence body composition and contribute to susceptibility for cardiometabolic disease.
We hypothesize that there will be both common variants and population specific variants that contribute to BMI and body fat distribution, and hence to an increased risk of obesity-related CMDs. By relating body fat distribution to environmental factors (e.g. diet, education levels, poverty) and genetic variation, whilst being mindful of the effects of infections (HIV, TB and malaria), it should be tractable to identify significant genetic determinants of body fat distribution and BMI. The relationship between body fat distribution and metabolic function will also be assessed. This could be used to mitigate the health transition across the African continent.
(Themes A, C; Collaborating components 1, 2 & 3)