Trans-ethnic meta-analysis of blood pressure in African and European ancestries

非洲和欧洲血统血压的跨种族荟萃分析

• 批准号: 8755381
• 负责人: Nora Franceschini
• 金额: $ 12.83万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8755381
• 关键词: Affect; African; African American; Aging; American Indians; Asians; Biological Markers; Blood Pressure; Cardiovascular Diseases; Chronic Kidney Failure; Clinical; Collaborations; Computer software; Coronary heart disease; Data; Development; Drug Targeting; Epidemiology; European; Gene Frequency; Genetic; Genetic Determinism; Genetic Variation; Genomics; Genotype; Goals; Health; Heart; Heritability; Heterogeneity; Hispanics; Hypertension; Individual; Japanese Population; Kidney; Kidney Diseases; Knowledge; Lead; Linkage Disequilibrium; Maps; Meta-Analysis; Methods; National Heart, Lung, and Blood Institute; Outcome; Pathway interactions; Pattern; Population; Population Heterogeneity; Prevention strategy; Reporting; Research; Resources; Risk; Sample Size; Sampling; Statistical Methods; Stroke; Subgroup; Variant; Work; base; blood pressure regulation; burden of illness; cardiovascular disorder risk; cohort; cost effective; disability; ethnic difference; gene discovery; genetic epidemiology; genetic variant; genome wide association study; hypertension treatment; improved; innovation; insight; mortality; novel; pleiotropism; public health relevance; racial and ethnic; racial and ethnic disparities; racial/ethnic difference; trait

DESCRIPTION (provided by applicant): Hypertension is a leading cause of global disease burden, mortality and disability, contributing to a greater risk of cardiovascular disease, stroke and chronic kidney disease. African Americans are disproportionally affected by hypertension and its complications. Whether these racial/ethnic differences in hypertension risk are related to genetic factors is currently unknown. Studies of individuals of diverse ancestry have provided evidence for presence of additional common variants in the population with broad effects across ancestries, which could be leveraged for gene discovery in trans-ethnic meta-analysis. Using genome wide association study data from the COGENT-BP and CHARGE-BP consortia, we propose to perform trans-ethnic meta-analyses of blood pressure traits in individuals of African and European ancestry for variant discovery and fine mapping of loci, by leveraging trans-ethnic differences in allele frequencies and the patterns of linkage disequilibrium. We will examine the evidence for association of the most significantly associated blood pressure variants with clinical relevant cardiovascular disease and kidney outcomes in collaborations with established consortia. Findings from this study could have a broad impact on gene discovery and fine mapping of loci, and may provide information on genetic determinants of racial/ethnic disparities to guide strategies for prevention and treatment of hypertension and its complications.

描述（由申请人提供）：高血压是全球疾病负担、死亡率和残疾的主要原因，导致心血管疾病、中风和慢性肾脏疾病的风险增加。非裔美国人受到高血压及其并发症的严重影响。高血压风险的这些种族/民族差异是否与遗传因素有关目前尚不清楚。对不同祖先个体的研究提供了证据，表明人群中存在其他常见变异，对不同祖先产生广泛影响，这可以用于跨种族荟萃分析中的基因发现。使用来自COGENT-BP和CHARGE-BP联盟的全基因组关联研究数据，我们建议通过利用等位基因频率和连锁不平衡模式的跨种族差异，对非洲和欧洲血统个体的血压性状进行跨种族荟萃分析，以发现变异和精细定位基因座。我们将研究最显著相关的血压变异与临床相关性的证据。 相关的心血管疾病和肾脏的结果与既定的财团合作。这项研究的结果可能对基因发现和基因座精细定位产生广泛影响，并可能提供种族/民族差异的遗传决定因素的信息，以指导高血压及其并发症的预防和治疗策略。