AWI-Gen Phase 2 - Overall component Abstract AWI-Gen is the Africa Wits-INDEPTH partnership for Genomic Studies, a 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 toward 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.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54HG006938-06
Application #
9386866
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Troyer, Jennifer L
Project Start
2012-08-15
Project End
2022-06-30
Budget Start
2017-09-14
Budget End
2018-06-30
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Wits Health Consortium (Pty), Ltd
Department
Type
DUNS #
639391218
City
Johannesburg
State
Country
South Africa
Zip Code
2193
Asiki, Gershim; Mohamed, Shukri F; Wambui, David et al. (2018) Sociodemographic and behavioural factors associated with body mass index among men and women in Nairobi slums: AWI-Gen Project. Glob Health Action 11:1470738
Pisa, Pedro T; Micklesfield, Lisa K; Kagura, Juliana et al. (2018) Different adiposity indices and their association with blood pressure and hypertension in middle-aged urban black South African men and women: findings from the AWI-GEN South African Soweto Site. BMC Public Health 18:524
Mulder, Nicola; Abimiku, Alash'le; Adebamowo, Sally N et al. (2018) H3Africa: current perspectives. Pharmgenomics Pers Med 11:59-66
Choudhury, Ananyo; Aron, Shaun; Sengupta, Dhriti et al. (2018) African genetic diversity provides novel insights into evolutionary history and local adaptations. Hum Mol Genet 27:R209-R218
Munthali, Richard J; Sahibdeen, Venesa; Kagura, Juliana et al. (2018) Genetic risk score for adult body mass index associations with childhood and adolescent weight gain in an African population. Genes Nutr 13:24
Sahibdeen, Venesa; Crowther, Nigel J; Soodyall, Himla et al. (2018) Genetic variants in SEC16B are associated with body composition in black South Africans. Nutr Diabetes 8:43
Gómez-Olivé, F Xavier; Rohr, Julia K; Roden, Laura C et al. (2018) Associations between sleep parameters, non-communicable diseases, HIV status and medications in older, rural South Africans. Sci Rep 8:17321
Haregu, T N; Mohamed, S F; Muthuri, S et al. (2018) Body mass index and wealth index: positively correlated indicators of health and wealth inequalities in Nairobi slums. Glob Health Epidemiol Genom 3:e11
Hendry, Liesl M; Sahibdeen, Venesa; Choudhury, Ananyo et al. (2018) Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort. BMC Med Genomics 11:2
Choudhury, Ananyo; Ramsay, Michèle; Hazelhurst, Scott et al. (2017) Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans. Nat Commun 8:2062

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