BCX-Africa: Utilizing data science to evaluate the applicability of blood cell traits polygenic risk scores for disease prediction in Africa

BCX-Africa：利用数据科学评估血细胞性状多基因风险评分在非洲疾病预测中的适用性

• 批准号: 10714228
• 负责人: Tinashe Chikowore
• 金额: $ 25.38万
• 依托单位: UGANDA VIRUS RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714228
• 关键词: Address; Africa; African; African American; African American population; African ancestry; Asian ancestry; Blood Cells; Blood Platelets; Cardiovascular Diseases; Collaborations; Collection; Communicable Diseases; Data; Data Discovery; Data Science; Data Set; Development; Diabetes Mellitus; Diagnosis; Disease; Disease Outcome; Disease susceptibility; East Asian; Elasticity; Environment; Erythrocytes; Ethnic Origin; Etiology; European; European ancestry; Evaluation; Exposure to; Funding; Genetic; Genetic Risk; Genetic Variation; Genetic study; Genomics; Goals; Health; Health Policy; Health Sciences; Hematological Disease; Heredity; Heritability; Human; Hypertension; Individual; Infection; Institution; Knowledge; Leukocytes; Linkage Disequilibrium; Machine Learning; Maps; Meta-Analysis; Mission; Modeling; Nigeria; Persons; Play; Polygenic Traits; Population; Predisposition; Public Health; Publishing; Research; Resolution; Resource-limited setting; Resources; Risk; Risk Factors; Role; Severity of illness; Shapes; Sickle Cell Anemia; Signal Transduction; Strategic Planning; Stroke; Techniques; Testing; Therapeutic; Training; Treatment outcome; United States National Institutes of Health; Variant; Work; case control; clinical phenotype; computing resources; convolutional neural network; drug development; gene discovery; genetic architecture; genetic association; genetic variant; genome analysis; genome resource; genome wide association study; genomic data; genomic locus; health data; improved; information gathering; insight; leukemia; multilayer perceptron; novel; open data; phenome; polygenic risk score; pressure; risk prediction; trait; working group

Project Summary The goal of the proposed work is to leverage existing genomic data of blood cell traits from the H3Africa and other initiative across Africa for novel gene discovery and genetic risk prediction in Africa ancestry individuals using DSI-Africa funded Open Data Science Platform (ODSP) which allows for effective collaborative research in a resource limited setting. Circulating blood cell traits are critical intermediate clinical phenotypes for a range of disease outcomes including cardiovascular, hematologic and infectious disease. Genetic factors play an important role in determining these traits. However, hundreds of genetic loci have been identified using conventional genome-wide association study (GWAS) approach in European and East Asian-ancestry populations. In view of the genetic diversity of Africans from other ancestries, and their low representation of 1.1% in global GWAS, more studies are required to unravel population specific variants that have been noted to exist in blood cell traits. Given the central importance of Africa to human origins and disease susceptibility, there is a clear scientific and public health need to develop large-scale efforts examining blood cell traits susceptibility in populations of African descent, which might yield insights that will benefit other ethnicities regarding disease etiology and potential therapeutic strategies. Specifically, we will aggregate blood cell traits GWAS data across continental Africa and African Americans leveraging existing partnership in Africa including H3Africa from ~35K individuals. We will test for association between genetic variants and 15 blood cell traits in a meta-analysis GWAS and refine genetic association signals at new and existing blood cell traits association loci. We will develop and assess transferability of Polygenic Risk Score (PRS) for blood cell traits risk in Africa including evaluating the predictivity of the blood cell traits PRS for a range of non-communicable diseases including leukaemia (N=5,926), Hypertension (N = 39,784), Stroke (N=5,540), Diabetes mellitus (N=20,506) and sickle cell disease (N= 5,704) in collaboration with participating non-academic partner on the project (54gene Lagos Nigeria). Our proposal is directly aimed at a key mission of RFA-RM-22-023, to support harnessing data science for health discovery, that will not only generate important findings relevant to human health, but also serve as a vehicle to improve the genomic data science research capacity in Africa. Our proposal also directly addresses the NIH strategic plan for data science. The unique collaboration within the Human Heredity and Health in Africa (H3Africa) for a cross-group analyse in Africa strengthen the capacity of scientific research through scientific training in all participating institution, which facilitate opportunity for shared expertise and resources.

项目摘要 拟议工作的目的是利用来自 H3AFRICA和其他非洲的其他倡议，用于新的基因发现和遗传风险预测 非洲血统的个人使用DSI-AFRICA资助的开放数据科学平台（ODSP） 在资源有限的设置中允许有效的协作研究。循环血细胞性状是 关键的中间临床表型，用于一系列疾病结局，包括心血管， 血液学和传染病。遗传因素在确定这些特征方面起着重要作用。 但是，使用常规全基因组关联鉴定了数百个遗传基因座 欧洲和东亚人口种群的研究（GWAS）方法。鉴于遗传 来自其他祖先的非洲人多样性及其在全球GWAS中的1.1％的低表现， 需要更多的研究来揭示已注意到中存在的特定于人群的变体 血细胞性状。鉴于非洲对人类起源和疾病易感性的核心重要性， 明确的科学和公共卫生需要开发检查血细胞的大规模努力 非洲血统人群中的特征易感性，这可能会产生有益的见解 有关疾病病因和潜在治疗策略的种族。具体来说，我们会的 在非洲大陆和非洲裔美国人的总体血细胞特征总计GWAS数据 非洲的现有合作伙伴关系，包括来自约35,000个人的H3africa。我们将测试关联 元分析中的遗传变异和15个血细胞性状之间 新的和现有的血细胞特征协会基因座的关联信号。我们将开发和评估 多基因风险评分（PRS）对于非洲血细胞性状风险的可转移性包括评估 血细胞性状PR的预测性PRS针对一系列非传染性疾病（包括） 白血病（n = 5,926），高血压（n = 39,784），中风（n = 5,540），糖尿病（n = 20,506） 与镰状细胞疾病（n = 5,704）与参与的非学术伴侣合作 项目（54Gene Lagos尼日利亚）。我们的建议直接针对RFA-RM-22-023的关键任务， 为了利用数据科学进行健康发现，这不仅会产生重要的发现 与人类健康相关，但也是改善基因组数据科学研究的工具 非洲的能力。我们的建议还直接解决了NIH数据科学战略计划。这 非洲人类遗传与健康中的独特合作（H3AFRICA） 非洲分析通过所有人的科学培训来增强科学研究的能力 参与机构，有助于共享专业知识和资源的机会。