Family Study of Stroke Risk and Carotid Atherosclerosis

描述（由申请人提供）：中风仍然是一个主要的公共卫生 这个问题对非洲裔美国人和西班牙裔美国人的影响不成比例。我们 对风险因素的了解有所改善，但现有数据有限 关于基因的影响。鉴于中风是一种复杂的疾病， 具有较大遗传力的风险因素表型的评估可能会降低 复杂性，促进基因发现，完善中风预防策略。 本申请的目的是评估新血管病变的遗传性。 危险因素（同型半胱氨酸、颈动脉内膜中层厚度（IMT）、颈动脉 扩张性、肱动脉内皮反应性和左心室质量）， 在来自北方曼哈顿的高风险加勒比西班牙裔家庭中， 卒中研究队列（NOMASS）。我们建议系统地衡量这些 定量表型，组装DNA家族研究数据库，执行基因组 扫描，并开始通过初步连锁鉴定数量性状基因座 分析.这将是第一个家庭研究的重点是迅速增长的 加勒比海西班牙裔族群。建议在100名 选择并入组高风险加勒比海西班牙裔家庭（1500例受试者） 超过四年。将进行入组和基线数据收集 如在基于人群的NOMASS方案（NINDS RO129993）中开发的。 将收集人口统计学、社会经济学、风险因素和饮食数据 通过使用标准化工具对家庭成员进行直接访谈。 将采集空腹血糖、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。所有受试者 将有高分辨率的B型超声成像来测量颈动脉IMT， 扩张性、肱动脉内皮反应性和左心室质量。 血沉棕黄层的储存和DNA的提取将由哥伦比亚 大学基因组中心和基因分型将在第四年和第五年由 遗传疾病研究中心。将进行统计分析 在哥伦比亚大学。遗传性将使用基于家系的 最大似然法将进行初步的连锁分析， 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.