Integrative nutrigenomic and metabolomic analyses of Africans with variable diets

 描述(由申请人提供)：大多数关于人类基因组变异、营养和代谢特征的研究都集中在非非洲人群上。然而，非洲是一个值得研究的重要地区，因为它是现代人的发源地。非洲是人类基因变异水平最高的地区，也是现代人类在世界范围内向非洲以外地区扩展的源头。几种常见的代谢性复杂疾病，如肥胖症、2型糖尿病和某些心血管疾病，在非裔美国人中发生的频率更高，而且在非洲的城市中心正在上升。据推测，这一点 这是由于基因变异适应了过去间歇性获取食物的环境，但不适应营养丰富的“西化”环境。代谢组学技术已经开始提供对代谢过程的洞察，并可用于识别疾病风险的生物标记物，并提供对与风险相关的代谢途径的洞察。鉴于营养和代谢以及随后的疾病风险之间的密切关系，代谢组学为营养研究提供了一个独特而强大的工具。在这项提案中，我们将利用代谢组图谱来询问一组独特的、种族多样化、表型良好的非洲土著人口的现存血浆，这些人从事不同的生存模式(农业、牧业、农牧业和狩猎-采集)，这些人心脏代谢风险的标志明显不同。我们将在365个人的样本中进行非定向代谢组学分析，并将在1500个不同种族的非洲人样本中有针对性地分析信息代谢物，以确定与饮食以及与疾病风险相关的人体测量学和心血管表型相关的代谢物和代谢途径的差异。我们将把这些数据与在同一个体中收集的大型全基因组单核苷酸多态(SNP)和全基因组序列数据集整合在一起，以深入了解遗传、营养和其他环境因素如何导致非洲不同种族人群心脏代谢风险特征的变异。

 DESCRIPTION (provided by applicant): Most studies of human genomic variation, nutrition, and metabolic traits have focused on non- African populations. However, Africa is an important region to study as it is the site of origin of modern humans. Africa contains the greatest levels o human genetic variation and is the source of the worldwide range expansion of modern humans to regions outside of Africa. Several common complex diseases of metabolic origin, such as obesity, type 2 diabetes and certain cardiovascular diseases occur at higher frequency in African Americans, and are on the rise in urban centers in Africa. It has been postulated that this is due to genetic variants adaptive for past environments with intermittent access to food but maladaptive in nutritionally replete "Westernized" environments. Metabolomics technology has begun to provide insight into metabolic processes and can be used for biomarker identification for disease risk and provide insight into metabolic pathways associated with risk. Given the intimate relationship between nutrition and metabolism and subsequent disease risk, metabolomics provides a unique and powerful tool in nutritional research. In this proposal, we will exploit metabolomic profiling to interrogate extant plasma from a unique set of ethnically diverse, well phenotyped indigenous African populations who practice different subsistence patterns (agriculture, pastoralism, agro- pastoralism, and hunting-gathering) who vary markedly in markers of cardiometabolic risk. We will perform untargeted metabolomics profiling in a sample of 365 individuals and will do targeted profiling of informative metabolites in a sample of 1500 ethnically diverse Africans to identify differences in metabolites and metabolic pathways that correlate with diet and anthropometric and cardiovascular phenotypes associated with disease risk. We will integrate these data with a large genome-wide Single Nucleotide Polymorphism (SNP) and whole genome sequence dataset collected in the same individuals to gain insight into how genetic, nutritional and other environmental factors contribute to variation in cardiometabolic risk traits in ethnically diverse African populations.