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性状的基因组数据， H3 Africa和非洲各地的其他新基因发现和遗传风险预测倡议， 非洲血统的个人使用DSI-Africa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合作研究。循环血细胞特征是 一系列疾病结果的关键中间临床表型， 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，使用常规的全基因组关联已经确定了数百个遗传位点 研究（GWAS）方法在欧洲和东亚血统的人群。鉴于遗传 来自其他祖先的非洲人的多样性，以及他们在全球GWAS中的低代表性， 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重要性， 有一个明确的科学和公共卫生需要发展大规模的努力， 性状的易感性在非洲裔人口，这可能会产生的见解，将有利于其他 关于疾病病因学和潜在治疗策略的种族差异。具体来说，我们将 非洲大陆和非裔美国人的GWAS数据汇总 非洲现有的合作伙伴关系，包括来自约3.5万人的H3非洲。我们将测试关联性 在荟萃分析GWAS中，遗传变异和15种血细胞性状之间的关系， 在新的和现有的血细胞性状关联基因座的关联信号。我们将开发和评估 非洲血细胞性状风险的多基因风险评分（PRS）的可转移性，包括评估 一系列非传染性疾病的血细胞特征PRS的预测性，包括 白血病（N=5,926）、高血压（N = 39,784）、卒中（N=5,540）、糖尿病（N=20,506） 和镰状细胞病（N= 5，704）与参与的非学术合作伙伴合作， 尼日利亚拉各斯54基因项目。我们的提案直接针对RFA-RM-22-023的关键使命， 支持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，也可以作为改善基因组数据科学研究的载体 非洲的能力。我们的提案还直接涉及NIH数据科学战略计划。的 在非洲人类遗传与健康（H3 Africa）的跨群体合作 通过对所有人进行科学培训，加强非洲的科学研究能力 参与机构，促进分享专门知识和资源的机会。

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.