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: 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
• 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

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

项目摘要 符合H3africa财团的目标和父母赠款（AWI-GEN）这项研究 旨在增加来自不同人群的非洲基因组数据，以确保不留下非洲 在基因组革命的背后。我们将专门针对以前未研究的人群 发现其他非洲遗传多样性并进行人群遗传研究 阐明了导致当前人口分布的迁移和混合事件 大陆。该研究分为三个阶段，每个阶段提供了更多信息， 全球研究界将可用的数据集。第一阶段将涉及 来自八个以前未研究的非洲人口（每个人50个人）的短读序列。 第二阶段将使每个人群的样本量增加到100，以更好地估计等位基因 频率，还将包括长阅读测序以构建非洲的参考图 人群提高变异通话准确性。第三阶段将评估转录组 和300个人的甲基化曲线，以深入了解 在全基因组关联研究中鉴定出的新型变体和变体。开发数据 更好地表示非洲遗传多样性，跨越了四个主要的民族语言学分歧 （Niger-Congo，Nilo-Saharan和Afro-Asiatic和North African）我们将专注于WGS 研究的地理区域（图1）。 WGS数据将集成到Open和 易于访问的资源，例如正在开发的非洲基因组变异数据库 h3abionet。我们将进行深度人口遗传分析，以更好地理解 大陆上的基因组多样性，迁移，混合和人口统计学的历史。这会 包括测试班图移民的各种替代模型，并将提供更好的 来自古代基因组数据的情境化。为了更好地组装短读 序列我们计划使用长阅读测序来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产生的全球努力 参考基因组。转录组和甲基化数据集将具有巨大的价值 推断新发现的变体的可能作用及其在健康和疾病中的相关性。 通过这个目标，我们将开始为非洲人口建立功能性的基因组资源 扩大全球努力的重点是EQTL识别，替代剪接和MEQTL。 1

项目成果

Polygenic risk scores for CARDINAL study.

• DOI: 10.1038/s41588-022-01074-3
• 发表时间: 2022-05
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Adebamowo, Clement A.;Adeyemo, Adebowale;Ashaye, Adeyinka;Akpa, Onoja M.;Chikowore, Tinashe;Choudhury, Ananyo;Fakim, Yasmina J.;Fatumo, Segun;Hanchard, Neil;Hauser, Michael;Mitchell, Braxton;Mulder, Nicola;Ofori-Acquah, Solomon F.;Owolabi, Mayowa;Ramsay, Michele;Tayo, Bamidele;VasanthKumar, Archana Bhavani;Zhang, Yuji;Adebamowo, Sally N.
• 通讯作者: Adebamowo, Sally N.

Bantu-speaker migration and admixture in southern Africa.

• DOI: 10.1093/hmg/ddaa274
• 发表时间: 2021-04-26
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Choudhury A;Sengupta D;Ramsay M;Schlebusch C
• 通讯作者: Schlebusch C

Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.

• DOI: 10.1038/s41467-022-30098-w
• 发表时间: 2022-05-11
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Choudhury A;Brandenburg JT;Chikowore T;Sengupta D;Boua PR;Crowther NJ;Agongo G;Asiki G;Gómez-Olivé FX;Kisiangani I;Maimela E;Masemola-Maphutha M;Micklesfield LK;Nonterah EA;Norris SA;Sorgho H;Tinto H;Tollman S;Graham SE;Willer CJ;AWI-Gen study;H3Africa Consortium;Hazelhurst S;Ramsay M
• 通讯作者: Ramsay M

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort.

• DOI: 10.1186/s12920-018-0321-6
• 发表时间: 2018-01-17
• 期刊: BMC medical genomics
• 影响因子: 2.7
• 作者: Hendry LM;Sahibdeen V;Choudhury A;Norris SA;Ramsay M;Lombard Z;of the AWI-Gen study and as members of the H3Africa Consortium
• 通讯作者: of the AWI-Gen study and as members of the H3Africa Consortium

Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans.

• DOI: 10.1038/s41467-022-28276-x
• 发表时间: 2022-02-14
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Boua PR;Brandenburg JT;Choudhury A;Sorgho H;Nonterah EA;Agongo G;Asiki G;Micklesfield L;Choma S;Gómez-Olivé FX;Hazelhurst S;Tinto H;Crowther NJ;Mathew CG;Ramsay M;AWI-Gen Study;H3Africa Consortium
• 通讯作者: H3Africa Consortium