Cohort Profile: Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen) in four sub-Saharan African countries

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Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen) was established to examine genomic, environmental and behavioural factors influencing body composition and cardiometabolic diseases and traits in African populations. Population-based longitudinal cohort, involving four sub-Saharan African countries representing rural and urban settings: West Africa [Nanoro (Burkina Faso) and Navrongo (Ghana)]; East Africa [Nairobi (Kenya)]; and South Africa (Agincourt, Dikgale/DIMAMO and Soweto). Baseline data collected from 2013 to 2017, enrolling 12 032 adults [55.1% women; mean (SD) 51.9 (8.3) years, range 37–82], with follow-up ∼5 years later and a retention rate of almost 60%. In Wave 2 an additional 579 individuals were enrolled (n = 7804; 55.9% women; 57.0 (7.9), 39–98). Main categories of data collected at two time points include sociodemographic characteristics, history of chronic diseases and lifestyle behaviours, with spirometry, cognition and frailty added in the second data collection wave. Measurements at both time points include anthropometry, blood pressure, carotid intima–media thickness and body fat distribution. Blood and urine samples are collected to measure biomarkers for diabetes, HIV, dyslipidaemia and kidney disease, and stool samples are collected in a women’s sub-sample for gut microbiome analyses. Genome-wide genotyping is available for all participants and whole genome sequences for a subset. We encourage collaboration, and data are accessible through the AWI-Gen Principal Investigator [[email protected]] in consultation with the steering committee or the H3Africa Data and Biospecimen Access Committee. Cardiometabolic diseases (CMDs) are on the rise worldwide and are leading causes of premature mortality,1 a trend also observed in low- and middle-income countries (LMICs) including those in Africa.2 There is a paucity of data from African countries on CMD prevalence, particularly on the genetic predisposition to common diseases, despite the recognition that African populations have high genetic diversity and unique population substructure.3–5 To address this gap, we set up the Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen). The AWI-Gen population cohort, initiated in 2012, was funded by the National Institutes of Health (NIH) as part of the Human Heredity and Health in Africa (H3Africa) Consortium.6 AWI-Gen is a collaboration between the University of the Witwatersrand (Wits) in Johannesburg and the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH). Five of the six study sites reside within existing health and demographic surveillance systems (HDSS). The remaining site is a Wits research unit in urban Soweto, Johannesburg. AWI-Gen’s main goal is to provide a research resource to investigate the prevalence of CMD and associated risk factors, and to explore gene–gene and gene–environment interactions.7,8 Additional aims are to strengthen the capacity for genomic research in Africa and to understand the key ethical, legal and sociocultural issues that would affect implementation. In 2012, a meeting was held with ethics committee members to consider appropriate models for informed consent, data sharing and community benefit.9 Community sensitization was followed by context-relevant stepwise permissions and individualized consent before entry into the study. The approach of broad consent for the future use of data and biological samples was agreed on by the research team and was also the preferred model adopted by H3Africa. The AWI-Gen process was documented at all sites, highlighting community engagement experiences and lessons learned.10,11 General health awareness and education were provided and point-of-care tests performed (glucose, lipids and HIV, the latter with supportive trained counsellors). Participants with health concerns (e.g. high blood pressure and high fasting glucose levels) were referred to the local health facilities with explanatory notes. Appropriate feedback was provided in reasonable time frames, and ongoing engagement and awareness of research progress were shared with communities. The longitudinal nature of the cohort permits assessment of changes in measurements and behaviour over about a 5-year period, and their impact on cardiometabolic endpoints. Knowledge gained from the AWI-Gen study has the potential for translational impact, including policy briefs and development of strategies for precision medicine applications in participating communities. AWI-Gen study participants are from five INDEPTH member HDSS centres in Africa, with diverse representation of populations from rural and urban environments in West, East and South Africa.7,8 These centres are Nanoro (Burkina Faso),12 Navrongo (Ghana),13 Nairobi (Kenya),14 Agincourt (South Africa)15 and Dikgale (later renamed DIMAMO) (South Africa)16 and the SAMRC/Wits Developmental Pathways for Health Research Unit (DPHRU) (Soweto, South Africa).17 The geographical location, number and biological sex distribution of participants from each study centre and a timeline for training, community engagement and recruitment, are shown in Figure 1, with study participant characteristics in Table 1. Description of the AWI-Gen study across two waves of data collection. (A) Location of the six study locations in health and demographic surveillance systems (HDSS) and the Developmental Pathways to Health Research Unit (DPHRU), showing the number of participants recruited in Wave 1 and the number recalled in Wave 2. Note that the DIMAMO cohort was enhanced in Wave 2 due to the lower recruitment numbers in Wave 1. (B) Number of men and women per study centre with the augmentation in DIMAMO shown with the cross-hatching. (C) Timeline showing community engagement that is still ongoing, and recruitment during Wave 1 and Wave 2. Recruitment started earlier in Soweto since we onboarded women from a study on menopause which was already on the files from 2012. Six PhD students graduated through the Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen) study and a further three are in progress. AWI-Gen meetings coincided with some of the Human Heredity and Health in Africa (H3Africa) consortium meetings, and training workshops were held to ensure that data were collected according to the same protocols and standard operating procedures. The colour coding per centre is consistent across all figures Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen) study site and study characteristics HDSS, health and demographic surveillance survey; SD, standard deviation. For the Soweto cohort, recall was finalized when 70% of participants had been recalled into Wave 2. Not all participants were recontacted. For the Dikgale/DIMAMO cohort an additional 579 participants were recruited in Wave 2. Africa Wits-INDEPTH partnership for Genomic studies (AWI-Gen) study site and study characteristics HDSS, health and demographic surveillance survey; SD, standard deviation. For the Soweto cohort, recall was finalized when 70% of participants had been recalled into Wave 2. Not all participants were recontacted. For the Dikgale/DIMAMO cohort an additional 579 participants were recruited in Wave 2. At baseline (Wave 1), AWI-Gen was a population-based cross-sectional survey that aimed to enrol 2000 participants, 40–60 years of age, approximately equal numbers of men and women, from each of the six study centres. Random sampling was used to select participants from existing populations based at the HDSS. Each study centre used mechanisms to minimize selection bias. Criteria excluded closely related individuals, pregnant women and individuals resident in the community for <10 years. Closely related individuals were considered first-degree relatives, but despite this, genetic analysis revealed significant relatedness among participants in some centres. Ethics approval was obtained from the Wits Human Research Ethics Committee (Medical) a

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