AWI-Gen Phase 2: Genomic and environmental risk factors for cardiometabolic disease in Africans

AWI-Gen 第 2 期：非洲人心脏代谢疾病的基因组和环境危险因素

• 批准号: 9386866
• 负责人: Michele Michele Ramsay
• 金额: $ 118万
• 依托单位: WITS HEALTH CONSORTIUM (PTY), LTD
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386866
• 关键词: Address; Admixture; Africa; Africa South of the Sahara; African; African American; Age; Aging; Algorithms; Animals; Architecture; Automobile Driving; Behavior; Behavioral; Bioinformatics; Biological Markers; Body Composition; Body fat; Burkina Faso; Communities; Computer Simulation; Country; Cross-Sectional Studies; Data; Data Collection; Data Set; Demographic Factors; Development; Diabetes Mellitus; Disease; Educational workshop; Elderly; Environmental Health; Environmental Risk Factor; Epidemiology; Epigenetic Process; Evaluation; Feedback; Foundations; Funding; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genome; Genomics; Genotype; Geography; Ghana; Goals; HIV; Health; Health Policy; Health Transition; Heredity; Heterogeneity; Human; Hypertension; Individual; International; Intervention; Kenya; Laboratories; Life Expectancy; Link; Linkage Disequilibrium; Longitudinal Studies; Longitudinal cohort; Malaria; Mathematics; Menopause; Meta-Analysis; Modeling; Morbidity - disease rate; Obesity; Participant; Pathway interactions; Personal Behavior; Phase; Phenotype; Physiological; Physiology; Play; Policies; Population; Predisposition; Prevalence; Prevention; Publishing; Randomized; Recording of previous events; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Role; SNP array; Sampling; Scientist; South Africa; Standardization; Structure; Students; Time; Training; United States National Institutes of Health; Universities; Visit; Wit; Woman; Work; base; burden of illness; cardiometabolic risk; cohort; community health study; comparative; disorder risk; gene environment interaction; genetic association; genetic risk assessment; genetic variant; genome wide association study; genome-wide; global environment; glucose tolerance; health inequalities; improved; insight; instrument; microbiome; middle age; mortality; population based; population health; predictive modeling; rural setting; sex; social; tool; trait; treatment strategy; trend; urban setting

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.

AWI-Gen阶段2-总体组件 摘要 AWI-Gen是非洲Wits-INDEPTH基因组研究伙伴关系，NIH资助的一所大学 支持非洲人类遗传与健康合作中心(H3非洲)联盟。这是一个 约翰内斯堡威特沃特斯兰德大学(WITS)与国际 人口及其健康人口评估网络(INDEPTH)。AWI-Gen检查 影响个体生理和行为的基因组和环境因素 非洲人群的身体成分、体脂分布以及心脏代谢性疾病和风险， 旨在为有效的预防、治疗和干预策略提供见解和证据。 用于为建模、预测和政策提供信息的经验性、经验证的非洲数据仍然匮乏，卫生保健领域正在扩大 尽管全球年龄标准化死亡率有所改善，但国家内部和国家之间的不平等现象仍然很明显 和发病率。AWI-Gen第一阶段是一项以人群为基础的横断面研究，研究平台超过 来自布基纳法索、加纳、肯尼亚和南非的12,045名40-60岁的参与者解决了这些问题 差距。我们四年的合作伙伴关系成功地产生了人口、环境、健康等方面的影响 一系列快速转型的非洲人的历史、行为、人体测量、生理和遗传数据 设置。 AWI-Gen合作中心提供了一个独特的资源来研究遗传关联和基因- 环境相互作用将有助于非洲中心风险预测模型和适合非洲的 孟德尔随机化工具，并开发其潜力，以改善个人和人口 卫生--同时加强区域研究能力。 我们的总体目标是确定基因组对心脏代谢性疾病和风险的影响 在存在高背景艾滋病毒或疟疾流行率的情况下，发生多个相互作用的转变 在整个非洲大陆推动了CMD的快速升级。加深我们对CMD和 关于非洲人口的风险，我们的目标是扩大数据收集并发展一个以人口为基础的“超级”队列(来自 跨地理环境的协调队列)，非常适合于检查中年人的进步 和老年人。我们制定了四个密切相关的研究项目：(1)遗传关联研究 通过检测关键蛋白阐明决定身体成分和CMD风险的功能通路 基因组和环境贡献者。(2)构建生物信息学分析工具分析资源 适用于非洲人口，包括遗传风险测定、孟德尔随机化工具 以及基因-环境交互作用算法。(3)检查体内绝经过渡的变化 组成和CMD风险因素，并评估生理、遗传和表观遗传导致的风险 透视。(4)检查老年人的微生物群及其与肥胖、糖尿病和血糖的关系 耐受性和更年期过渡引起的CMD风险。 我们假设，存在非洲特有的基因-环境相互作用，这是导致 整个非洲大陆正在展开健康转型，这种环境影响的表观遗传和 微生物群的变化起着重要作用。艾滋病毒和疟疾将在我们的模型中考虑，因为它们可能 具有批判性影响。我们在AWI-Gen阶段2中对女性的重视来自于日益增长的流行率 在妇女中，特别是在流行病学转变较远的地区，肥胖和相关疾病的发病率 路径。非洲的基因组研究具有独特的潜力，可以利用较低水平的连锁不平衡 在非洲基因组中对相关基因进行精细定位，以识别原因基因和变异，并指导功能 对候选地区的分析。我们的第一个项目为西部队列的发展奠定了基础-- 东南非研究遗传变异、环境、社会 以及人口统计因素、个人行为和近端危险因素对身体成分和易感性的影响 致CMD。这将是撒哈拉以南非洲的第一项多种族研究，以解决 在过渡的力量正在推动心脏新陈代谢状况上升的时候进行理解。 我们希望这些发现与我们的大陆背景高度相关，并为我们提供更多见解 广泛地。