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; 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是非洲Wits-Stepth基因组研究的伙伴关系，是NIH资助和大学 支持非洲人类遗传与健康的协作中心（H3africa）财团。是一个 威特沃特斯兰大学，约翰内斯堡（WITS）和国际的战略伙伴关系 人群评估人口及其健康的网络（Indepth）。 AWI-GEN考试 与个体生理学和行为相互作用的基因组和环境因素 身体成分，体内脂肪分布和心脏代谢疾病以及非洲人口的风险， 旨在提供有效预防，治疗和干预策略的见解和证据。 经验，经过验证的非洲数据，以告知建模，项目和政策仍然很少并扩大健康 不平等是国家内部和国家之间的证据，目的地全球改善了年龄标准化的死亡率 和发病率。 Awi-Gen阶段1是一项基于人群的横断面研究 12,045名参与者来自布基纳法索，加纳，肯尼亚和南非40 - 60年 差异。我们的四年合作伙伴关系成功地产生了Epi人口统计学，环境，健康 在一系列快速过渡的非洲人的历史，行为，人体测量学，身体和遗传数据 设置。 AWI-GEN协作中心提供了一种独特的资源来检查遗传关联和基因 环境互动将有助于以非洲为中心的风险预测模型和适合非洲的环境 孟德尔随机仪器，并利用其潜力来改善个人和人口 健康 - 同时增强了区域研究能力。 我们的总体目标是建立对心脏代谢疾病和风险的基因组贡献 当多个相互作用的过渡（在高背景HIV或疟疾患病率的存在下）是 在整个非洲大陆的CMD中迅速升级。加深我们对CMD和 非洲人口的风险，我们旨在扩展数据收集并开发基于人群的“超级”队列（来自 跨地理环境的协调组）非常适合研究中年的发展 和老年人。我们已经开发了四个密切相关的研究项目：（1）遗传关联研究与 通过检测关键来确定身体组成和CMD风险涉及的功能途径 基因组和环境贡献者。 （2）建立生物信息学分析工具的分析资源 适合非洲人口，包括遗传风险确定，孟德尔随机工具 和基因 - 环境相互作用算法。 （3）检查身体更年期过渡的变化 组成和CMD风险因素，并评估物理，遗传和表观遗传学的风险 观点。 （4）检查老年人的微生物组及其与肥胖，糖尿病和葡萄糖的关系 耐受性和CMD风险由更年期过渡引起。 我们假设存在非洲特定的基因环境相互作用，这是 整个非洲大陆的健康转变，环境影响了表观遗传和 微生物组变化起着重要作用。艾滋病毒和疟疾将在我们的模型中考虑 有关键的影响。我们对AWI-GEN第2阶段中女性的重视是由于越来越多的流行而引起的 妇女的肥胖和相关病毒性，尤其是在流行病学转变的地区 小路。非洲的基因组研究具有利用较低链接dissequibrium的独特潜力 在非洲基因组中，用于鉴定因果基因和变异的相关局部的精细映射，并引导功能 候选区域的分析。我们的第一个项目为West- 东南非洲检查遗传变异，环境，社会的独特和相互作用的影响 以及人体组成和易感性的人口因素，个人行为和近端风险因素 到CMD。这将是撒哈拉以南非洲的首次多民族研究，以解决严重的短缺 在过渡力推动心脏代谢条件下增加的时期。 我们希望发现在我们的持续内容中具有很高的相关性，并能够贡献更多的见解 广泛。