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: 7430295
• 负责人: James Graham Wilson
• 金额: $ 69.24万
• 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/7430295
• 关键词: Admixture; Affect; African; African American; Age; American; Appendix; Biological Markers; Birth Records; Birth Weight; Blood; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chromosome Mapping; Cohort Studies; Commit; Complex; Coronary Arteriosclerosis; DNA; Data; Data Analyses; Development; Diabetes Mellitus; Diet; Disease; Drug Delivery Systems; Environmental Risk Factor; European; Family Study; Fasting; Frequencies; Genes; Genetic; Genetic Risk; Genome; Genome Scan; Genotype; Glucose; Heart; Heart failure; Hypertension; Individual; Institutes; Invasive; Language; Lead; Left Ventricular Hypertrophy; Lipids; Localized; Low Birth Weight Infant; Lung; Malignant neoplasm of prostate; Maps; Measures; Medical; Medical History; Methods; Mississippi; Morbidity - disease rate; Multiple Sclerosis; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Osteoporosis; Participant; Phenotype; Physical activity; Predisposition; Prevalence; Process; Publishing; Rate; Research; Research Personnel; Resources; Risk; Sampling; Sampling Studies; Scanning; Serum; Stroke; Testing; Time; Woman; Work; cancer type; cardiovascular disorder risk; case control; cohort; density; disease phenotype; disorder risk; experience; follow-up; genetic analysis; genetic linkage analysis; genetic resource; genome wide association study; health disparity; men; mortality; positional cloning; programs; success; trait

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较小的基因之间的相互作用。在识别此类基因方面，关联作图比连锁作图强大得多，但需要 200-500 倍的标记来扫描基因组。混合作图可以发挥关联研究的大部分作用，但只需要对全基因组范围内的几千个标记进行基因分型。该应用程序与杰克逊心脏研究 (JHS) 的研究人员以及混合物绘图领域的两位领导者 Drs. 合作。大卫·赖克和尼克·帕特森。拟议的研究将利用布罗德研究所的基因分型和分析能力，在有史以来规模最大的非裔美国人心血管疾病研究队列中进行混合图谱分析。有几个因素促成了这项研究的及时性，并显示了拟议研究团队的实力：（a）我们的小组发表了第一个用于混合作图的实用遗传资源：非洲人和欧洲人之间频率差异较大的 2,154 个标记，以及分析数据的方法。 (b) 我们组建了一个独特的队列，对 CVD 风险基因进行有史以来最大规模的全基因组混合扫描：对 3,796 名无关的非裔美国人进行了严格的大量 CVD 表型特征分析，包括高血压、冠状动脉疾病、中风、糖尿病和心力衰竭。 (c) 混合图谱首次取得经验性成功，定位了高血压和多发性硬化症的基因。混合图谱在实践中发挥了作用，因此应用它来寻找 JHS 队列中的 CVD 基因至关重要。我们提出了三个具体目标： 具体目标 1：CVD 相关基因的全基因组混合扫描。我们将在 DMA 中输入来自 JHS 队列的 3,796 名不相关的非裔美国参与者的 3,072 个混合映射标记。我们将集中分析非洲裔美国人和欧洲人之间已知患病率差异的表型：高血压、血脂水平、左心室肥大和低出生体重。具体目标 2：跟踪和精细绘制两个最强关联峰。我们将在 940 名参与者中对 2,535 个额外的 SNP/峰值进行基因分型（所选表型的每个极端为 470 个）。具体目标 3：获取 JHS 参与者的所有记录的出生体重。通过混合作图，出生体重将作为 CVD 表型的协变量和独立表型进行分析。 Lav语言描述：寻找影响疾病风险的基因可以确定药物治疗的新靶点，并导致重要医学测试的发展。这些研究将寻找导致非洲裔美国人心脏和血管疾病的非洲和欧洲基因。