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
基本信息
- 批准号:10714228
- 负责人:
- 金额:$ 25.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAfricaAfricanAfrican AmericanAfrican American populationAfrican ancestryAsian ancestryBlood CellsBlood PlateletsCardiovascular DiseasesCollaborationsCollectionCommunicable DiseasesDataData DiscoveryData ScienceData SetDevelopmentDiabetes MellitusDiagnosisDiseaseDisease OutcomeDisease susceptibilityEast AsianElasticityEnvironmentErythrocytesEthnic OriginEtiologyEuropeanEuropean ancestryEvaluationExposure toFundingGeneticGenetic RiskGenetic VariationGenetic studyGenomicsGoalsHealthHealth PolicyHealth SciencesHematological DiseaseHeredityHeritabilityHumanHypertensionIndividualInfectionInstitutionKnowledgeLeukocytesLinkage DisequilibriumMachine LearningMapsMeta-AnalysisMissionModelingNigeriaPersonsPlayPolygenic TraitsPopulationPredispositionPublic HealthPublishingResearchResolutionResource-limited settingResourcesRiskRisk FactorsRoleSeverity of illnessShapesSickle Cell AnemiaSignal TransductionStrategic PlanningStrokeTechniquesTestingTherapeuticTrainingTreatment outcomeUnited States National Institutes of HealthVariantWorkcase controlclinical phenotypecomputing resourcesconvolutional neural networkdrug developmentgene discoverygenetic architecturegenetic associationgenetic variantgenome analysisgenome resourcegenome wide association studygenomic datagenomic locushealth dataimprovedinformation gatheringinsightleukemiamultilayer perceptronnovelopen dataphenomepolygenic risk scorepressurerisk predictiontraitworking group
项目摘要
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.
项目概要
拟议工作的目标是利用现有的血细胞特征基因组数据
H3Africa 和非洲其他地区的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),该平台
允许在资源有限的环境中进行有效的合作研究。循环血细胞的特征是
一系列疾病结果的关键中间临床表型,包括心血管、
血液学和感染性疾病。遗传因素在决定这些性状方面发挥着重要作用。
然而,使用传统的全基因组关联已经鉴定了数百个遗传位点
欧洲和东亚血统人群的全基因组关联研究(GWAS)方法。鉴于遗传
来自其他血统的非洲人的多样性,以及他们在全球 GWAS 中所占比例低至 1.1%,
需要更多的研究来解开已被注意到存在于人群中的特定变异
血细胞特征。鉴于非洲对于人类起源和疾病易感性至关重要,
显然,科学和公共卫生需要开展大规模的血细胞检查工作
非洲人后裔人群的特征易感性,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
利用非洲大陆和非裔美国人的 GWAS 数据汇总血细胞特征
非洲现有的合作伙伴关系,包括来自约 35,000 个人的 H3Africa。我们将测试关联性
在荟萃分析 GWAS 中分析遗传变异和 15 种血细胞特征之间的关系,并细化遗传
新的和现有的血细胞性状关联位点的关联信号。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
血细胞特征 PRS 对一系列非传染性疾病的预测能力,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)
和镰状细胞病 (N= 5,704) 与参与的非学术合作伙伴合作
项目(54gene 拉各斯尼日利亚)。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,同时也可以作为改进基因组数据科学研究的工具
非洲的能力。我们的提案还直接涉及 NIH 数据科学战略计划。这
非洲人类遗传与健康 (H3Africa) 内部的独特跨群体合作
分析非洲通过科学培训加强科学研究能力
参与机构,促进共享专业知识和资源的机会。
项目成果
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