Thrombosis genetics in African Americans
非裔美国人的血栓形成遗传学
基本信息
- 批准号:9309925
- 负责人:
- 金额:$ 80.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-20 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:African AmericanAmericanAnticoagulantsArterial Fatty StreakAtherosclerosisBioinformaticsBiological MarkersBiologyBloodBlood VesselsBlood coagulationCD14 geneCardiovascular DiseasesCause of DeathClinicalCoagulation ProcessCodeComplement Factor DComplexDataData SetDiseaseDisease OutcomeEnvironmental Risk FactorEpidemiologyEthnic OriginEthnic groupEuropeanEventFactor VIIIFactor VIIaFactor XIIFactor XIaFibrin fragment DFibrinogenFibrinolytic AgentsGenerationsGeneticGenetic studyGenomicsHealthHemorrhageHemostatic functionHeritabilityInflammationInflammatoryInterleukin 2 ReceptorIschemic StrokeJackson Heart StudyKnowledgeLaboratoriesMeasurementMeasuresMediationMinorityModalityMulti-Ethnic Study of AtherosclerosisMyocardial InfarctionNational Heart, Lung, and Blood InstituteParticipantPathway interactionsPhenotypePlasmaPopulationPopulation GeneticsPredispositionRaceReasons for Geographic And Racial Differences in StrokeRiskRisk FactorsRoleRuptureSafetySample SizeSamplingSignal TransductionStrokeSystemTherapeuticThrombinThromboplastinThrombosisThrombusTrans-Omics for Precision MedicineUnited StatesValidationVariantVenousVenous Thrombosisbasecardiovascular disorder riskcardiovascular healthcohortcoronary artery calcificationdatabase of Genotypes and Phenotypesethnic disparitygamma Fibrinogengenetic approachgenetic associationgenetic variantgenome wide association studygenome-widegeographic differencehealth disparityin vivoinnovationinterestintimal medial thickeningnovelnovel markernovel strategiesracial differenceracial disparityrare variantrisk variantvascular inflammationwhole genome
项目摘要
ABSTRACT
Cardiovascular diseases are the leading cause of death in the United States, and
disproportionate rates are seen in minority African American populations. Thrombosis and
vascular inflammation are important contributors to atherosclerotic plaque rupture and vascular
occlusion that underlie myocardial infarction, ischemic stroke, as well as venous
thromboembolic disease. The identification of novel biomarkers and their assessment in
different ethnic populations can augment the information obtained from traditional CVD risk
factors as well as illuminate underlying disease mechanisms and health disparities. While blood
biomarkers have been shown to be critically important in the study of CVD, there is a deficit of
studies of these measures in African American populations. Preliminary data suggest that
thrombin generation, as quantified ex vivo by plasma measurement of endogenous thrombin
potential (ETP) is a novel approach to understanding the connection of both the intrinsic and
extrinsic coagulation pathways to thrombus formation in vivo. Whole genome sequence (WGS)
data, including both coding and functional noncoding variants, are required to identify the full
spectrum of contributions of rare variants to common diseases. WGS data are particularly
important among non-European ancestry groups, where there is still relatively limited genomic
information. Using stored baseline Jackson Heart Study (JHS) plasma samples from 3,500
African Americans, we propose to measure several emerging thrombosis and inflammation
plasma biomarkers (endogenous thrombin potential, fibrinogen gamma', coagulation factors VIII
and VIIa, soluble interleukin-2 receptor, soluble CD14, and soluble CD163) that are likely to
reflect and/or account for increased thrombogenicity and therefore may contribute to higher
rates of CVD in African Americans. We will assess the association of thrombosis biomarkers
and biomarker-associated genetic variants with more complex subclinical and clinical CVD
endpoints available in JHS and other African American cohorts, including REGARDS. By adding
these key measures of thrombosis and inflammation to the JHS and REGARDS data sets,
utilizing existing whole genome sequence data available through the NHLBI TOPMed project,
and using innovative analytical and population genetic approaches, we will be able to greatly
expand our knowledge of the role of thrombosis and inflammation in CVD health disparities.
摘要
心血管疾病是美国人死亡的主要原因,
非裔美国少数民族的发病率不成比例。血栓形成和
血管炎症是动脉粥样硬化斑块破裂和血管炎的重要因素
心肌梗塞、缺血性中风以及静脉血栓形成的基础
血栓栓塞性疾病新的生物标志物的鉴定及其在
不同种族人群可以增加从传统CVD风险中获得的信息,
这些因素以及阐明潜在的疾病机制和健康差距。同时血液
生物标志物已被证明是至关重要的CVD的研究,有一个赤字,
在非裔美国人中进行这些措施的研究。初步数据显示,
凝血酶生成,通过内源性凝血酶的血浆测量离体定量
电位(ETP)是一种新的方法来理解的内在和
外源性凝血途径与体内血栓形成。全基因组序列
数据,包括编码和功能非编码变体,需要识别完整的
罕见变异对常见疾病的贡献谱。WGS的数据尤其
在非欧洲祖先群体中,这一点很重要,那里的基因组仍然相对有限,
信息.使用来自3,500名患者的储存基线杰克逊心脏研究(JHS)血浆样本,
非裔美国人,我们建议测量几个新兴的血栓形成和炎症
血浆生物标志物(内源性凝血酶潜能、纤维蛋白原γ、凝血因子VIII
和VIIa,可溶性白细胞介素-2受体,可溶性CD 14和可溶性CD 163),其可能
反映和/或说明血栓形成性增加,因此可能导致较高的
非裔美国人的心血管疾病发病率。我们将评估血栓形成生物标志物
和生物标志物相关的遗传变异与更复杂的亚临床和临床CVD
JHS和其他非裔美国人队列中可用的终点,包括REGARDS。通过添加
这些血栓形成和炎症的关键指标与JHS和REGARDS数据集,
利用NHLBI TOPMed项目提供的现有全基因组序列数据,
利用创新的分析和群体遗传学方法,我们将能够大大
扩大我们对血栓形成和炎症在CVD健康差异中的作用的认识。
项目成果
期刊论文数量(0)
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Leslie A Lange其他文献
Leslie A Lange的其他文献
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