Health Disparities and CVD: Admixture Mapping in the Jackson Heart Study

健康差异和 CVD：杰克逊心脏研究中的混合图谱

• 批准号: 7077078
• 负责人: James Graham Wilson
• 金额: $ 74.82万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-22 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7077078
• 关键词: African American; European; cardiovascular disorder epidemiology; clinical research; gene expression; genetic markers; genetic susceptibility; health disparity; health services research tag; human birth weight; human genetic material tag; human subject; hypertension; linkage mapping; lipid metabolism; single nucleotide polymorphism; ventricular hypertrophy

DESCRIPTION (provided by applicant): Genetic risk for complex processes like CVD appears to involve interactions among multiple genes of small effect. Association mapping is much more powerful than linkage mapping in identifying such genes, but requires 200-500 times as many markers to scan the genome. Admixture mapping can extract much of the power of association studies but requires genotyping only a few thousand markers genome-wide. This application partners Jackson Heart Study (JHS) investigators with two leaders in the field of admixture mapping, Drs. David Reich and Nick Patterson. The studies proposed will exploit the genotyping and analytic power of the Broad Institute to perform admixture mapping in the largest cohort ever assembled to study CVD in African Americans. Several factors contribute to the timeliness of this study and show the strength of the proposed research team: (a) Our group has published the first practical genetic resource for admixture mapping: 2,154 markers with large frequency differences between Africans and Europeans, and methods to analyze the data. (b) We have assembled a unique cohort for the largest-ever genome-wide admixture scan for CVD risk genes: 3,796 unrelated African Americans rigorously characterized for a large number of CVD phenotypes, including HTN, coronary artery disease, stroke, diabetes mellitus, and heart failure. (c) Admixture mapping has had its first empiric successes, localizing genes for hypertension and multiple sclerosis. Admixture mapping works in practice, making it critically important to apply it to seek CVD genes in the JHS cohort. We propose three specific aims: Specific Aim 1: Whole-genome admixture scanning for CVD related genes. We will type 3,072 admixture mapping markers in DMA of 3,796 unrelated African American participants from the JHS cohort. We will concentrate our analyses on phenotypes with known differences in prevalence between African Americans and Europeans: hypertension, serum lipid levels, left ventricular hypertrophy, and low birth weight. Specific Aim 2: Follow-up and fine-mapping of the two strongest peaks of association. We will genotype 2,535 additional SNPs/peak in 940 participants (470 at each extreme for the selected phenotype). Specific Aim 3: Acquire all recorded birth weights for JHS participants. Birth weight will be analyzed both as a covariate for CVD phenotypes and as an independent phenotype, by admixture mapping. Lav language description: Finding genes that affect the risk of disease can identify new targets for drug treatment and lead to the development of important medical tests. These studies will seek genes of African and European origin that cause heart and blood vessel diseases in African Americans.

描述（由申请人提供）：CVD等复杂过程的遗传风险似乎涉及多个效应的多个基因之间的相互作用。关联映射比识别此类基因的链接映射要强大得多，但需要扫描基因组的200-500倍。混合映射可以提取大部分关联研究的力量，但只需基因分型几千个标记范围的基因组。该应用程序合作伙伴杰克逊心脏研究（JHS）研究人员与混合映射领域的两名领导者，博士。大卫·赖希（David Reich）和尼克·帕特森（Nick Patterson）。提出的研究将利用广泛研究所的基因分型和分析能力，以在有史以来最大的同类人群中进行混合映射，以研究非裔美国人的CVD。几个因素有助于这项研究的及时性，并显示了拟议的研究团队的强度：（a）我们的小组发表了第一个用于混合映射的实用遗传资源：2,154个标志物在非洲人和欧洲人之间具有较大频率差异，以及分析数据的方法。 （b）我们为CVD风险基因的有史以来最大的全基因组混合物扫描组装了独特的队列：3,796名无关的非洲裔美国人对大量CVD表型进行了严格的特征，包括HTN，冠状动脉疾病，冠状动脉疾病，中风，糖尿病，糖尿病，糖尿病和心力衰竭。 （c）混合图取得了首次经验成功，将基因定位为高血压和多发性硬化症。混合映射在实践中起作用，因此将其应用于JHS队列中的CVD基因至关重要。我们提出了三个特定目标：特定目标1：针对CVD相关基因的全基因组混合扫描。我们将在DMA中键入3,072个混合映射标记，为3,796名来自JHS队列的非裔美国人参与者。我们将把分析集中在非裔美国人和欧洲人之间患病率的已知差异的表型上：高血压，血清脂质水平，左心室肥大和低出生体重。特定目标2：两个最强峰值峰的随访和细微映射。我们将在940名参与者中进行基因型2,535个额外的SNP/峰（对于选定的表型，每个极端的470个）。特定目标3：为JHS参与者获得所有记录的出生权重。通过混合映射，将分析出出生体重作为CVD表型的协变量和独立表型。 LAV语言描述：寻找影响疾病风险的基因可以识别用于药物治疗的新靶标，并导致重要的医疗测试的发展。这些研究将寻求非洲和欧洲血统的基因，这些基因在非洲裔美国人中引起心脏和血管疾病。