AWI-Gen 2: Genomic and Environmental Risk Factors for Cardiometabolic Disease in Africans

Principal Investigator

Prof Michele Ramsay

Abstract: AWI-Gen is the Africa Wits-INDEPTH partnership for Genomic Studies, an NIH funded and university supported Collaborative Center of the Human Heredity and Health in Africa (H3Africa) Consortium. It is a strategic partnership between the University of the Witwatersrand, Johannesburg (Wits), and the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH). AWI-Gen examines genomic and environmental factors that interact with individual physiology and behaviors to influence body composition, body fat distribution and cardiometabolic disease and risk in African populations, with the aim to provide insights and evidence towards effective prevention, treatment and intervention strategies. Empirical, validated African data to inform modeling, projections and policy remain scant and widening health inequalities are evident within and between countries, despite global improvements in age-standardized mortality and morbidity. AWI-Gen Phase 1 is a population-based cross-sectional study with a research platform of over 12,045 participants 40-60 years from Burkina Faso, Ghana, Kenya and South Africa that addresses these disparities. Our four-year partnership has successfully generated epi-demographic, environmental, health history, behavioral, anthropometric, physiological and genetic data across a range of rapidly transitioning African settings. The AWI-Gen Collaborative Center provides a unique resource to examine genetic associations and gene- environment interactions that will contribute to Afrocentric risk prediction models and African-appropriate Mendelian Randomization instruments, and exploit their potential to improve personal and population health – while strengthening regional research capacity. Our overall goal is to establish the genomic contribution to cardiometabolic disease and risk at a time when multiple interacting transitions, in the presence of high background HIV or malaria prevalence, are driving a rapid escalation in CMD across the African continent. To deepen our understanding of CMD and risk in African populations, we aim to extend data collection and develop a population-based `super’ cohort (from harmonized cohorts across geographic settings) that is well-suited to examining progression among middle-aged and older persons.

We have developed four closely linked research projects:

  1. Genetic association studies to elucidate functional pathways involved in determining body composition and risk for CMD by detecting pivotal genomic and environmental contributors.
  2. Building an analytic resource of bioinformatics analysis tools appropriate for African populations, including genetic risk determination, Mendelian Randomization instruments and gene-environment interaction algorithms.
  3. Examining changes over the menopausal transition in body composition and CMD risk factors, and evaluating the resulting risk from physiological, genetic and epigenetic perspectives.
  4. Examining the microbiome in older adults and its relationship to obesity, diabetes and glucose tolerance, and CMD risks arising from the menopausal transition.


We hypothesize that there are African-specific gene-environment interactions that are key drivers of the health transitions unfolding across the continent, and that environmentally influenced epigenetic and microbiome changes play an important role. HIV and malaria will be considered in our models as they may have critical influences. Our emphasis on women in AWI-Gen Phase 2 is informed by the increasing prevalence of obesity and associated morbidities in women, especially in regions farther along an epidemiological transition path. Genomic research in Africa has the unique potential to harness the lower levels of linkage disequilibrium in African genomes for fine mapping of associated loci to identify causal genes and variants, and guide functional analysis in candidate regions. Our first project provides the foundation for the development of cohorts in west- east-south Africa to examine the distinct and interacting influences of genetic variation, environmental, social and demographic factors, personal behaviors, and proximal risk factors on body composition and susceptibility to CMD. This will be the first multi-ethnic study in sub-Saharan Africa to address a critical shortfall in understanding at a time when the force of transitions is driving the rise in cardiometabolic conditions. We expect findings to be highly relevant in our continental context and to contribute insights far more widely

Related Projects

October 16, 2018

AWI-GEN 2: Genomic and Environmental Risk Factors for Cardiometabolic Disease in Africans

AWI-Gen is the Africa Wits-INDEPTH partnership for Genomic Studies, an NIH funded and university supported Collaborative Center of the Human Heredity and Health in Africa
April 6, 2018

Eyes of Africa: The Genetics of Blindness

“Eyes of Africa: The Genetics of Blindness” will address the staggering economic, societal, and personal cost of irreversible blindness in Africa. The most common cause of permanent
April 4, 2018

Genomic Characterization and Surveillance of Microbial Threats in West Africa

Overall Recent viral outbreaks in West Africa, specifically the 2013-16 Ebola Virus Outbreak, shed light on the many limitations of current surveillance and diagnostics in the region’s public health systems. Tools for rapid, accurate
April 4, 2018

Genomic and Environmental Risk Factors for Cardiometabolic Disease in Africans

The long-term vision of the Collaborative Centre (CC) is to build sustainable capacity in Africa for research that leads to an understanding of the interplay between genetic, epigenetic and
April 4, 2018

SickleGenAfrica: Sickle Cell Disease Genomics Network of Africa

Sickle cell disease (SCD) is the commonest genetic disorder in the World. It is most prevalent in Africa. We have established SickleGenAfrica:Sickle Cell Disease Genomics Network of Africa to build capacity locally to enable African scientists study genomics of SCD on the continent
April 4, 2018

Center for Research on the Respiratory Microbiota of African Children (ReMAC)

Center for Research on the Respiratory Microbiota of African Children (ReMAC): Abstract The microbiota (community of microorganisms) of the upper airways plays a key role in the development of lower respiratory tract infection (LRTI) in children. Most of the important bacterial LRTI pathogens also colonize the
April 4, 2018

Stroke Investigative Research & Educational Network (SIREN)

troke is the leading cause of neurological hospital admissions and a leading cause of deaths in Africa. Indeed, with an estimated stroke incidence of up to 315/100,000 population, about 6 Africans develop stroke every minute. Up to 3.2 million Africans develop first-incident stroke every year. Moreover, the burden
April 4, 2018

Collaborative African Genomics Network (CAfGEN)

Advanced genetic and genomic technologies promise to transform our understanding and approach to human health and disease. Such genomic analyses are now common in Western populations of European descent.
April 4, 2018

H3Africa Kidney Disease Research Network

It is estimated more than 500,000 individuals succumb to end stage renal disease annually in sub-Saharan Africa with an additional 50 million people suffering from pre-dialysis chronic kidney disease. Advanced genome-based analysis strategies, such as