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

描述(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更大。非裔美国人不成比例地受到高血压及其并发症的影响。目前尚不清楚高血压风险的种族/民族差异是否与遗传因素有关。对不同血统的个体的研究提供了证据，证明在种群中存在其他常见的变异，对祖先有广泛的影响，这可以用于跨种族荟萃分析中的基因发现。利用来自Coent-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，对非洲和欧洲血统的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。我们将研究最显著的血压变异与临床相关的证据。 与已建立的财团合作的相关心血管疾病和肾脏结果。这项研究的结果可能会对基因发现和基因座精细定位产生广泛的影响，并可能提供关于种族/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。

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.