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

基本信息

批准号：
10405680
负责人：
Michele Michele Ramsay
金额：
$ 76.41万
依托单位：
WITS HEALTH CONSORTIUM (PTY), LTD
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-14 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405680
关键词：
Address Administrative Supplement Admixture Africa African Alternative Splicing Architecture Award Biological Assay Cardiometabolic Disease Cardiovascular system Communities Congo Country DNA Data Data Analyses Data Set Databases Development Disease Ensure Environmental Risk Factor Ethnic group Event Gene Frequency Generations Genetic Population Study Genetic Variation Genome Genomics Geographic Locations Geography Grant Graph Health Individual Light Mendelian randomization Methylation Modeling Niger Nucleic Acids Parents Participant Phase Population Population Distributions Population Genetics Population Heterogeneity Recording of previous events Research Resources Role Sample Size Sampling Structure Techniques Testing Variant Whole Blood base cost functional genomics genetic analysis genetic risk assessment genome resource genome sequencing genome wide association study genome wide methylation genomic data improved insight metabolic phenotype methylome migration novel parent grant reference genome tool transcriptome transcriptome sequencing transcriptomics whole genome

项目摘要

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

项目概要本研究符合 H3Africa 联盟和家长资助 (AWI-Gen) 的目标旨在增强来自不同人群的非洲基因组数据，以确保非洲不被遗弃落后于基因组革命。我们将专门针对以前未研究过的人群发现更多的非洲遗传多样性并进行群体遗传学研究，这将揭示了导致当前人口分布的迁移和混合事件大陆。该研究分三个阶段提出，每个阶段都提供更多信息和将可供全球研究界使用的数据集。第一阶段将涉及来自八个之前未研究过的非洲人群（每个人群 50 个人）的短读序列。第二阶段将把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，以构建非洲的参考图群体，以提高变异调用的准确性。第三阶段将评估转录组学和 300 名个体的甲基化图谱，以深入了解全基因组关联研究中发现的新变异和变异。开发数据更好地代表跨越四个主要民族语言部门的非洲遗传多样性（尼日尔-刚果、尼罗-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、易于获取的资源，例如正在开发的非洲基因组变异数据库 H3A生物网。我们将进行深入的群体遗传分析，旨在更好地了解非洲大陆的基因组多样性、迁徙、混合和人口历史。这会包括测试班图迁移的各种替代模型，并将提供更好的来自古代基因组的数据的情境化。为了更好地组装短读我们计划使用长读长测序对这些基因组的子集进行测序技术（PacBio）。该数据集将有助于其他旨在生成参考基因组。转录组和甲基化数据集将具有巨大的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基因组资源加强全球重点关注 eQTL 识别、可变剪接和 meQTL 的努力。 1

项目成果

期刊论文数量（86）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Runs of homozygosity: windows into population history and trait architecture.

纯合性运行：了解种群历史和性状结构的窗口。

DOI：
发表时间：
2018
期刊：
影响因子：
0
作者：
Ceballos, Francisco C;Joshi, Peter K;Clark, David W;Ramsay, Michèle;Wilson, James F
通讯作者：
Wilson, James F

Sociodemographic and behavioural factors associated with body mass index among men and women in Nairobi slums: AWI-Gen Project.

与内罗毕贫民窟男性和女性体重指数相关的社会人口学和行为因素：AWI-Gen 项目。

DOI：
发表时间：
2018
期刊：
影响因子：
2.6
作者：
Asiki, Gershim;Mohamed, Shukri F;Wambui, David;Wainana, Caroline;Muthuri, Stella;Ramsay, Michelle;Kyobutungi, Catherine;as members of AWI
通讯作者：
as members of AWI

Genetic variants in SEC16B are associated with body composition in black South Africans.

SEC16B 的遗传变异与南非黑人的身体成分有关。

DOI：
发表时间：
2018
期刊：
影响因子：
6.1
作者：
Sahibdeen, Venesa;Crowther, Nigel J;Soodyall, Himla;Hendry, Liesl M;Munthali, Richard J;Hazelhurst, Scott;Choudhury, Ananyo;Norris, Shane A;Ramsay, Michèle;Lombard, Zané
通讯作者：
Lombard, Zané

C679X loss-of-function PCSK9 variant is associated with lower fasting glucose in black South African adolescents: Birth to Twenty Plus Cohort.

C679X 功能丧失 PCSK9 变异与南非黑人青少年的空腹血糖较低相关：出生至二十岁以上队列。

DOI：
发表时间：
2019-06
期刊：
影响因子：
0
作者：
Chikowore, Tinashe;Sahibdeen, Venesa;Hendry, Liesl M;Norris, Shane A;Goedecke, Julia H;Micklesfield, Lisa K;Lombard, Zané
通讯作者：
Lombard, Zané

Classical Cardiovascular Risk Factors and HIV are Associated With Carotid Intima-Media Thickness in Adults From Sub-Saharan Africa: Findings From H3Africa AWI-Gen Study.

经典心血管危险因素和 HIV 与撒哈拉以南非洲成年人的颈动脉内膜中层厚度相关：H3Africa AWI-Gen 研究的结果。

DOI：
发表时间：
2019
期刊：
影响因子：
5.4
作者：
Nonterah, Engelbert A;Boua, Palwende R;Klipstein;Asiki, Gershim;Micklesfield, Lisa K;Agongo, Godfred;Ali, Stuart A;Mashinya, Felistas;Sorgho, Herman;Nakanabo;Debpuur, Cornelius;Kyobutungi, Catherine;Alberts, Ma
通讯作者：
Alberts, Ma