GENOMIC AND ENVIRONMENTAL RISK FACTORS FOR CARDIOMETABOLIC DISEASE IN KENYA, AWI-Gen PHASE II

The Genomic and environmental risk factors for cardiometabolic disease in Africans (AWI-Gen) project was a collaborative study between the University of the Witwatersrand (Wits) and the INDEPTH Network funded under the Human Heredity and Health in Africa (H3Africa) initiative. The H3Africa was a ground-breaking initiative to build institutional and individual capacity to undertake genetic and genomic studies in the African region. This collaboration, involved five INDEPTH sites i.e. 1) Navrongo - Ghana; 2) Nanoro - Burkina Faso; 3&4) Agincourt and Digkale - South Africa; and 5) Nairobi - Kenya) plus the Soweto-based birth-to-twenty cohort. AWI-Gen phase I was a population based cross-sectional study with a research platform of over 12,045 participants aged 40-60 years from Burkina Faso, Ghana, Kenya and South Africa. It aimed to understand the interplay between genetic, epigenetic and environmental risk factors for obesity and related cardiometabolic diseases (CMD) in sub-Saharan Africa and it generated epi-demographic, environmental, health history, behavioral, anthropometric, physiological and genetic data across a range of rapidly transitioning African settings. This provided 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. We plan to continue this work in AWIGEN-phase II among the same participants recruited in AWIGen-I offering an opportunity to examine data in a longitudinal manner.
The AWI-Gen phase II project aims to establish the genomic contribution to CMD 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. The project capitalizes on the unique strengths of existing longitudinal cohorts and well-established health and demographic surveillance systems(HDSS) run by the partner institutions. The six study sites represent geographic and social variability of African populations which are also at different stages of the demographic and epidemiological transitions. The work in Kenya will be undertaken in the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) run by African Population and Health Research Center (APHRC) following participants who were recruited in AWIGEN-Phase I.
AWI-Gen II consisted of five main aims: i) AIM-1 (Sub-study 1): Genetic associations studies to elucidate functional pathways involved in determining body composition and risk for CMD by detecting pivotal genomic and environmental contributors; ii) AIM 2 (Sub-study 2): Genomics and bioinformatics-impact of genomic diversity on disease risk and precision public health; iii) AIM 3 (Sub-study 3): Examine changes over the menopausal transition in body composition and CMD risk; iv) AIM 4 (Sub-study 4): Examine gut microbiome in older adults and its relationship to obesity, diabetes and glucose tolerance and ageing; and v) AIM 5 (Sub-study 5): Explore respiratory disease in context of multi-morbidity.
In this application, we sought ethical approval for the Kenya study only. The other partners sought approval from their appropriate ethics review authorities in their countries. The study budget was $248,613 and was funded by National Institute of Health (NIH)-USA under H3Africa. Data collection was undertaken for approximately 12 months but sample processing, data analysis, manuscript writing, capacity building and policy engagement was continued up to three years after field work (up to 2022).