Family Study of Stroke Risk and Carotid Atherosclerosis

描述(申请人提供)：中风仍然是一种主要的公共卫生问题 对非裔美国人和西班牙裔美国人的影响不成比例的问题。我们的 对风险因素的了解有所提高，但可用的数据有限 关于基因的影响。鉴于中风是一种复杂的疾病， 遗传力较大的风险因素表型评估可能会减少 复杂性，促进基因发现，并完善中风预防策略。 这项应用的目的是评估新血管的遗传性。 危险因素(同型半胱氨酸、颈动脉内中膜厚度、颈动脉 扩张性、臂内皮细胞反应性和左心室重量)， 在来自曼哈顿北部的高危加勒比海拉美裔家庭中 卒中研究队列(NOMASS)。我们建议系统地衡量这些因素 定量表型，组装DNA家族研究数据库，执行基因组 扫描，并通过初步连锁开始识别数量性状基因座 分析。这将是第一个关注快速增长的家庭的研究 加勒比海西班牙裔族群。建议在100个家庭中进行一项家庭研究 高危加勒比拉美裔家庭(1500名受试者)被选中并登记 四年多了。将执行登记和基准数据收集 如以人口为基础的NOMASS议定书(NINDS ROL 29993)所制定的。 将收集人口、社会经济、风险因素和饮食数据 使用标准化工具对家庭成员进行直接访谈。 采血测定空腹血糖、电解质、肌酐、总 血清同型半胱氨酸和相关代谢物，以及血脂谱。所有科目 将有高分辨率的B型超声成像来测量颈动脉IMT和 扩张性、臂内皮细胞反应性和左心室重量。 棕黄色大衣的储存和DNA的提取将由哥伦比亚号完成 大学基因组中心和基因分型将在第四至第五年完成 遗传病研究中心。将进行统计分析 在哥伦比亚大学。遗传力将使用基于系谱的方法进行评估 最大似然法。将进行初步的连锁分析，以 确定与这些表型相关的数量性状基因座。

DESCRIPTION (provided by applicant): Stroke remains a major public health problem with a disproportionate impact on African Americans and Hispanics. Our knowledge of risk factors has improved, while only limited data are available regarding genetic influences. Given that stroke is a complex disease, evaluation of risk factor phenotypes with greater heritability may reduce complexity, facilitate gene discovery, and refine stroke prevention strategies. The goal of this application is to evaluate the heritability of new vascular risk factors (homocysteine, carotid intima-media thickness (IMT), carotid distensibility, brachial endothelial reactivity, and left ventricular mass), among the families of high-risk Caribbean Hispanics from the Northern Manhattan Stroke Study cohort (NOMASS). We propose to systematically measure these quantitative phenotypes, assemble a DNA family study databank, perform a genome scan, and begin to identify quantitative trait loci through preliminary linkage analysis. This will be the first family study focused on the rapidly growing Caribbean Hispanic race-ethnic group. A family study is proposed among 100 high-risk Caribbean Hispanic families (1500 subjects) selected and enrolled over four years. The enrollment and baseline data collection will be performed as developed in the population-based NOMASS protocol (NINDS ROl 29993). Demographic, socioeconomic, risk factor, and dietary data will be collected through direct interview of family members using standardized instruments. Blood will be collected for fasting glucose, electrolytes, creatinine, total serum homocysteine and related metabolites, and lipid profiles. All subjects will have high-resolution B-mode ultrasound imaging to measure carotid IMT and distensibility, brachial endothelial reactivity, and left ventricular mass. Storage of buffy coats and extraction of DNA will be done by the Columbia University Genome Center and genotyping will be done in year four-five by the Center for Inherited Disease Research. Statistical analysis will be conducted at Columbia University. Heritability will be evaluated using a pedigree-based maximum-likelihood method. Preliminary linkage analysis will be performed to identify quantitative trait loci linked to these phenotypes.