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

项目摘要 根据H3非洲联盟和父母补助金（AWI-Gen）的目标，本研究 旨在增加来自不同人群的非洲基因组数据，以确保非洲不会被遗忘， 落后于基因组革命。我们将专门针对以前未研究的人群， 发现更多的非洲遗传多样性，并进行人口遗传研究， 揭示了导致目前人口分布的迁移和混合事件， 大陆这项研究分三个阶段进行，每个阶段提供更多的信息， 这些数据集将提供给全球研究界。第一阶段将涉及 来自8个以前未研究过的非洲人群（每个人50个）的短阅读序列。 第二阶段将每个群体的样本量增加到100，以更好地估计等位基因 频率，还将包括长读测序，以建立非洲的参考图， 群体以提高变异识别准确性。第三阶段将评估转录组学 和甲基化谱，以深入了解 在全基因组关联研究中鉴定的新变体和变体。开发数据， 更好地代表非洲的遗传多样性，跨越四个主要的民族语言划分 （刚果、尼罗河-撒哈拉、亚非和北非）我们将重点关注WGS， 未充分研究的地理区域（图1）。WGS数据将被整合到一个开放的， 容易获得的资源，如非洲基因组变异数据库正在开发的 H3ABioNet。我们将进行深入的人口遗传分析，旨在更好地了解 基因组多样性、迁移、混合和非洲大陆的人口历史。这将 包括测试班图迁移的各种替代模型，并将提供更好的 将来自古代基因组的数据进行情境化。为了更好地组装短读 我们计划使用长读测序对这些基因组的一个子集进行测序 技术（PacBio）。这一数据集将有助于其他全球努力， 参考基因组转录组学和甲基化数据集将在以下方面具有巨大价值： 推断新发现的变异的可能作用及其与健康和疾病的相关性。 通过这一目标，我们将开始为非洲人口建立功能性基因组资源。 加强全球在eQTL鉴定、选择性剪接和meQTL方面的努力。 1

Project Summary In line with the objectives of the H3Africa Consortium and the parent grant (AWI-Gen) this study aims to augment African genomic data from diverse populations to ensure that Africa is not left behind in the genomic revolution. We will specifically target previously unstudied populations to discover additional African genetic diversity and to perform population genetic studies that will shed light on migration and admixture events that led to the current population distribution on the continent. The research is proposed in three phases, each providing more information and datasets that will become available to the global research community. This first phase will involve short-read sequences from eight previously unstudied African populations (50 individuals each). The second phase will increase the sample size per population to 100, to better estimate allele frequencies, and will also include long-read sequencing to build reference graphs for African populations to improve variant calling accuracy. The third phase will assess the transcriptomic and methylation profiles in 300 individuals to provide insight into the functional interpretation of novel variants and variants identified in genome-wide association studies. To develop data for better representation of African genetic diversity spanning the four major ethnolinguistic divisions (Niger-Congo, Nilo-Saharan and Afro-Asiatic and North African) we will focus on WGS from understudied geographic regions (Figure 1). The WGS data will be integrated into an open and easily accessible resource such as the African Genome Variation database being developed by H3ABioNet. We will perform in depth population genetic analyses aimed at a better understanding of genomic diversity, migration, admixture and demographic history on the continent. This would include testing various alternative models for the Bantu-migration and will provide a better contextualization of data from ancient genomes. To enable a better assembly of short-read sequences we plan to sequence a subset of these genomes using a long-read sequencing technique (PacBio). This dataset would contribute to other global efforts aimed at generating reference genomes. The transcriptomic and methylation datasets will be of immense value in inferring the possible roles of newly discovered variants and their relevance in health and disease. Through this objective we will start building a functional genome resource for African populations to augment global efforts focused on eQTL identification, alternate splicing and meQTLs. 1