Genes,Blood Pressure Variability and Cardiovascular Diseases

 描述(申请人提供)：流行病学研究表明，血压变异性的长期增加与心血管损害有关，并与心血管事件和死亡率的增加无关，与平均血压的升高无关。关于遗传学在高血压中的作用，有令人信服的数据。常见的基因变异和动脉血压变异性之间的关系以前从未在任何美国人群中进行过测试。这项拟议研究的具体目的是：目的A)定位与来访血压变异性相关的SNP。假设A)存在与就诊到就诊血压变异性相关的SNP。目的B)寻找同时调节来访间血压变异性和平均动脉压的共享SNPs。假设B)存在共同的SNPs，它们同时调节来访之间的血压变异性和平均动脉压。目的c)寻找共同调控来访血压变异性和心血管疾病的SNPs。假设C)存在共同的SNPs，它们调节来访之间的血压变异性和心血管疾病。为了实现上述目标，我们将分析心血管健康研究和妇女健康倡议研究的全基因组联合数据；我们计划使用(1)混合线性模型，(2)主成分和(3)随机效应韩氏-埃斯金模型来调整人口分层和考虑种族基因异质性。这项研究具有创新性： (1)还没有人发现同时调节来访间血压变异性和平均动脉压的SNPs。(2)我们首次尝试将共有的SNPs映射到来访的血压变异性和心血管疾病(Pleiotroy)之间。这项拟议的研究很重要，因为这些变异和基因区域的发现是揭示生物学洞察的垫脚石 确定降低血压变异性的新的药理学目标；这反过来将导致新的预防策略，以减少与血压变异性相关的心血管疾病日益增长的公共卫生负担。

 DESCRIPTION (provided by applicant): Epidemiologic studies revealed that long-term increases in blood pressure variability are associated with cardiovascular damage, and with an increased incidence of cardiovascular events and mortality independent of elevated mean blood pressure. There are compelling data on the role of genetics in hypertension. The relationship between common genetic variants and arterial blood pressure variability has not been tested before in any American population. The specific aims of the proposed study are: Aim A) To locate SNPs associated with Visit-to-Visit Blood Pressure Variability. Hypothesis A) There are SNPs associated with Visit-to-Visit Blood Pressure Variability. Aim B) To locate shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Mean Arterial Blood Pressure. Hypothesis B) There are shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Mean Arterial Blood Pressure. Aim C) To locate shared SNPs regulating both Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases. Hypothesis C) There are shared SNPs that regulate both Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases. To achieve the previously stated aims, we will analyze the Genome-Wide-Association data of Cardiovascular Health Study and Women's Health Initiative studies; we plan to use (1) Mixed Linear Models, (2) Principle components, and (3) Random Effect Han's-Eskin's models to adjust for population stratification and account for racial-genes heterogeneity. This study is innovative: (1) No one has ever located SNPs regulating both Visit-to-Visit Blood Pressure Variability and Mean arterial blood pressure. (2) We are trying to map shared SNPs between Visit-to-Visit Blood Pressure Variability and Cardiovascular Diseases (Pleiotropy) for the first time. The proposed study is important because the discovery of such variants and genetic regions is a stepping stone to uncover biological insights to identify new pharmacological targets for decreasing blood pressure variability; this in turn will lead to novel prevention strategies to reduce the growing public health burden of blood pressure variability-related cardiovascular disease.