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

项目摘要 拟议工作的目标是利用现有的血细胞特征基因组数据 H3非洲和非洲各地的其他倡议，以发现新的基因和预测遗传风险 使用DSI的非洲血统个人-非洲资助的开放数据科学平台(ODSP) 允许在资源有限的情况下进行有效的协作研究。循环中的血细胞特征是 一系列疾病结局的关键中间临床表型，包括心血管疾病， 血液病和传染病。遗传因素在决定这些性状中起着重要作用。 然而，使用传统的全基因组关联已经确定了数百个遗传位点。 欧洲和东亚血统人群的研究方法。从遗传角度来看 来自其他祖先的非洲人的多样性，以及他们在全球全球气候变化系统中所占比例较低，仅为1.1%， 需要更多的研究来解开已经注意到存在于 血细胞特征。鉴于非洲对人类起源和疾病易感性的核心重要性， 科学和公共卫生方面显然需要开展大规模的血细胞检测工作。 非洲人后裔群体中的特征易感性，这可能会产生有益于其他人的见解 关于疾病病因和潜在治疗策略的种族。具体来说，我们将 汇总非洲大陆和非洲裔美国人的血细胞特征数据 在非洲的现有合作伙伴关系，包括H3非洲，来自约35K人。我们将测试关联性 遗传变异与15个血细胞性状之间的Meta分析 关联信号位于新的和现有的血细胞特性关联基因座。我们将制定和评估 非洲血细胞特征风险多基因风险评分的可转移性，包括评估 血细胞特性PR对一系列非传染性疾病的预测性 白血病(N=5926)、高血压(N=39784)、中风(N=5540)、糖尿病(N=20506) 和镰状细胞病(N=5,704)与参与的非学术伙伴合作 项目(54基因拉各斯，尼日利亚)。我们的建议直接针对RFA-RM-22-023的一项关键任务， 为了支持利用数据科学进行健康发现，这不仅将产生重要的发现 与人类健康相关，但也是改进基因组数据科学研究的载体 非洲的运力。我们的提案还直接涉及NIH的数据科学战略计划。这个 在非洲人类遗传与健康(H3非洲)内为一个跨群体进行独特的合作 在非洲通过所有人的科学培训加强科学研究能力 参与机构，这为分享专业知识和资源提供了机会。

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.