National Institute of Environmental Health Sciences

By Janelle Weaver, Ph.D.

The detailed methods used for Phase 1 of a study of cardiovascular and metabolic disease in sub-Saharan Africa were published in a special issue of Global Health Action. The so-called AWI-Gen study, which is partly funded by NIEHS, could lead to the discovery of novel biomarkers and the development of new strategies to prevent and treat a growing health epidemic in Africa.

“Given the paucity of research into the genomic risk for noncommunicable diseases in African populations, the AWI-Gen study provides a unique resource to explore genetic associations with cardiometabolic risk factors and endpoints in sub-Saharan Africa,” said Michèle Ramsay, Ph.D., senior author of the study design article, head of the AWI-Gen study, and professor at the University of the Witwatersrand (Wits) in Johannesburg, South Africa.

Growing Crisis

Deaths from noncommunicable diseases are on the rise in sub-Saharan 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 behavior. 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.

In response to the global epidemic of noncommunicable diseases, the World Health Organization (WHO) proposed an action plan that includes nine voluntary targets, such as achieving a 25% relative reduction in premature mortality from cardiovascular diseases, cancer, diabetes, or chronic respiratory diseases by 2025. Another target aims for a 25% relative reduction in the prevalence of raised blood pressure, with the goal of halting the rise of obesity and diabetes. But large-scale data from Africa are needed to assess progress toward attaining these targets.

The main goal of the AWI-Gen study is to shed light on the prevalence of cardiometabolic disease, associated risk factors, and regional burden, and to explore gene-gene and gene-environment interactions that contribute to disease risk. The study was established in 2012 through a partnership between Wits and the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH). It is funded by the National Institutes of Health as part of the Human Heredity and Health in Africa (H3Africa) consortium.

“The genome data from AWI-Gen will enable one of the first sub-Saharan African-wide studies of the genetics of cardiometabolic diseases and associated risk factors and will be a baseline study for other genomics studies,” said Kimberly McAllister, Ph.D., a health science administrator in the Genes, Environment, and Health Branch at NIEHS.

“There is the potential for discovery of novel disease-related associations and novel gene-environment and gene-gene discoveries that might help better understand the rapid rise of these complex common diseases in African populations,” added McAllister, who also co-leads NIEHS involvement in the H3Africa consortium. “This study provides a baseline for the future development of many additional studies that can dig deeper into the genetic and environmental risk factors associated with cardiometabolic disease in Africa.”

Treasure Trove

In the article, the researchers describe the detailed methods for data and sample collection, as well as quality control measures, undertaken during Phase 1 of the AWI-Gen study. The goal of the first phase is to assess risk factors and endpoints for cardiovascular and metabolic disease in adults over the age of 40 across six centers in West Africa, East Africa, and South Africa. From 2012 to 2016, a total of 11,723 individuals participated in the study, providing blood and urine samples, as well as heath data through questionnaires.

The researchers used the specimens for disease-related biomarker assays, and for genomic DNA extraction for genome-wide association studies. They also assessed sociodemographic and anthropometric factors, medical history, diet, physical activity, fat distribution, and alcohol and tobacco consumption. “The breadth of data we have obtained will allow us to determine associations with disease and modifiable factors such as BMI [body-mass index], fat distribution and physical activity, together with biomarkers of disease and disease endpoints,” Ramsay said.

According to Ramsay, the success of the study was due to the experience of the research team, its attention to community engagement, and the development of processes for broad consent and storage of data and specimens, including DNA, for future use. Initially, the main challenges were related to establishing acceptable norms and obtaining ethics approval for such a large-scale genomics study. It was also necessary to make appropriate cultural adaptations across countries and in rural and urban settings.

But this effort is already paying dividends. Baseline data generated from this study has resulted in several publications, including a collection of papers on BMI distribution across African communities in the special issue of Global Health Action. In addition, the detailed methods will enable opportunities for further harmonization with other studies.

Moving forward, the researchers plan to revisit participants in Phase 1 of the AWI-Gen study in several years to evaluate the progression of cardiometabolic disease trajectories. In Phase 2 of the study, they will implement electronic data collection, point-of-care testing for glucose and cholesterol, expanded questionnaires, and additional analyses of menopause-related changes and the microbiome. “The data generated from the AWI-Gen study could be used for improved modelling of noncommunicable disease risk in Africa in different regions and in a global health context, and this may contribute to the development of policies more appropriate to sub-Saharan Africa,” Ramsay said.