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 第 2 阶段 - 整体组件 抽象的 AWI-Gen 是 Africa Wits-INDEPTH 基因组研究合作伙伴，是 NIH 资助的大学 支持非洲人类遗传与健康合作中心 (H3Africa) 联盟。它是一个 约翰内斯堡威特沃特斯兰德大学 (Wits) 与国际组织之间的战略伙伴关系 人口及其健康人口统计评估网络 (INDEPTH)。 AWI-Gen 检查 与个体生理和行为相互作用以影响的基因组和环境因素 非洲人群的身体成分、体脂肪分布以及心脏代谢疾病和风险， 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过验证的非洲经验数据仍然不足，而且健康状况正在扩大 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仍然很明显 和发病率。 AWI-Gen 第一阶段是一项基于人群的横断面研究，拥有超过 来自布基纳法索、加纳、肯尼亚和南非的 12,045 名 40-60 岁参与者讨论了这些问题 差异。我们四年的合作伙伴关系已成功产生了流行人口、环境、健康 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 合作中心提供了独特的资源来检查遗传关联和基因- 环境相互作用将有助于建立以非洲为中心的风险预测模型和适合非洲的 孟德尔随机化工具，并利用其潜力来改善个人和人口 健康——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疾病和风险的贡献 当多重相互作用的转变，在高背景艾滋病毒或疟疾流行的情况下， 导致整个非洲大陆的 CMD 迅速升级。加深我们对 CMD 的理解 非洲人口的风险，我们的目标是扩大数据收集范围并开发一个基于人口的“超级”队列（来自 跨地理环境的协调队列）非常适合检查中年人的进展 和老年人。我们开发了四个密切相关的研究项目：（1）遗传关联研究 通过检测关键因素来阐明参与确定身体成分和 CMD 风险的功能途径 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 适合非洲人群，包括遗传风险测定、孟德尔随机化工具 和基因-环境相互作用算法。 (3)检查更年期过渡期间身体的变化 成分和 CMD 危险因素，并从生理、遗传和表观遗传角度评估由此产生的风险 观点。 (4) 检查老年人的微生物组及其与肥胖、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与环境的相互作用，这是非洲经济发展的关键驱动因素。 整个非洲大陆正在发生健康转型，环境影响着表观遗传和 微生物组的变化发挥着重要作用。我们的模型中将考虑艾滋病毒和疟疾，因为它们可能 具有重要影响。我们在 AWI-Gen 第 2 阶段对女性的重视是因为患病率不断上升 女性肥胖及相关发病率，尤其是在流行病学转变较远的地区 小路。非洲的基因组研究具有利用较低水平的连锁不平衡的独特潜力 在非洲基因组中对相关基因座进行精细定位，以识别因果基因和变异，并指导功能 候选区域的分析。我们的第一个项目为西方队列的发展奠定了基础 东南非研究遗传变异、环境、社会的独特和相互作用的影响 人口因素、个人行为以及对身体成分和易感性的近端风险因素 到命令。这将是撒哈拉以南非洲地区第一项多种族研究，旨在解决 在转变的力量推动心脏代谢状况上升的时代，我们必须了解这一点。 我们期望研究结果与我们大陆的背景高度相关，并提供更多见解 广泛。