Epidemiologic Architecture for Genes Linked to Environment (EAGLE)

环境相关基因的流行病学结构 (EAGLE)

• 批准号: 7658897
• 负责人: DANA C CRAWFORD
• 金额: $ 168.91万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-17 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658897
• 关键词: Accounting; African; Age related macular degeneration; Alleles; American; Architecture; Cardiovascular Diseases; Centers for Disease Control and Prevention (U.S.); Chemicals; Clinical; Clinical Data; Collection; Communities; Complex; Contracts; Coronary Arteriosclerosis; Cotinine; Cross-Sectional Studies; DNA; Data; Data Set; Development; Diet; Disease; Elderly; Electron Transport; Ensure; Environment; Environmental Exposure; Equipment; European; Family; Female; Frequencies; Funding; Future; General Population; Genes; Genetic; Genetic Research; Genetic Variation; Genome; Genotype; Glucose; Grant; Haplotypes; Health; Health Status; Human; Human Genetics; Human Genome; Human Genome Project; Individual; Inflammation; International; Investments; Laboratories; Life Style; Link; Literature; Maps; Measurement; Measures; Metabolic; Methods; Mexican Americans; Minority; Mitochondria; Modeling; National Health and Nutrition Examination Survey; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Nuclear; Obesity; Outcome; Participant; Pharmaceutical Preparations; Phase; Phenotype; Physical Examination; Physical activity; Physicians; Population; Population Attributable Risks; Population Heterogeneity; Positioning Attribute; Predisposition; Preventive Intervention; Proteins; Public Health; Questionnaires; Reporting; Request for Applications; Research; Research Personnel; Resources; Rheumatoid Arthritis; Risk; SNP genotyping; Sampling; Staging; Standardization; Statistical Methods; Surveys; System; Testing; Translating; United States National Center for Health Statistics; Universities; Variant; Visit; base; case control; cigarette smoking; cigarette smoking; clinical phenotype; cohort; cost; demographics; disease phenotype; gene environment interaction; gene interaction; genetic association; genome wide association study; human disease; interest; lipid metabolism; novel; pesticide exposure; population based; research study; sex; statistics; trait; translational study

DESCRIPTION (provided by applicant): With the advent of the Human Genome Project, the International HapMap Project, and high-throughput yet cost-effective genotyping, it is now possible to interrogate the human genome with >1 million markers for associations with common human diseases and traits. Within the last few months, the literature has become inundated with reports of genome-wide association (GWA) studies identifying new genetic variations associated with phenotypes of public health interest. While the flurry of discovery is exciting, the usefulness of these new findings in a general population setting remains unclear. Therefore, the next steps beyond the initial GWA studies must provide population-based data on these initial associations before the most promising findings can be translated into improvements in intervention, prevention, and/or treatment options for the general population. The genetic component of the National Health and Nutrition Examination Surveys (NHANES; n~20,000) can provide the data necessary to move beyond the initial GWA study discoveries. NHANES is a U.S. population-based, cross-sectional survey collected by the Centers for Disease Control and Prevention. NHANES DNAs are linked to demographic, health, lifestyle, laboratory, extensive clinical, and physical examination data for participating individuals. Because participants are ascertained regardless of health status, NHANES is a rich resource for phenotypes (clinical endpoints and quantitative traits) and environmental exposures. With this large dataset, the epidemiologic architecture of GWA-identified genetic variations will be described, and association studies will be conducted to provide more accurate effect size estimates and population attributable fractions for many common diseases and traits such as type 2 diabetes, obesity, and coronary artery disease. Finally, tests for gene-environment and nuclear mitochondrial gene interactions will be performed, the latter of which laboratory data will be generated to support the statistical association. The purpose of this grant is to provide evidence in population-based datasets that GWA-identified genetic variations are relevant to most people. As such, GWA-identified variations will be characterized and population-based statistics and data for modifiers of these variations will be released rapidly so that the most promising findings can be incorporated into future translational studies by the research community.

描述（由申请人提供）：随着人类基因组项目的出现，国际HAPMAP项目和高通量却具有成本效益的基因分型，现在可以使用> 100万个标记来审问人类基因组，以与共同的人类关联疾病和特征。在过去的几个月中，文献已被全基因组关联（GWA）研究所淹没，这些研究鉴定了与公共卫生兴趣表型相关的新遗传变异。虽然发现的范围令人兴奋，但这些新发现在一般人口环境中的有用性尚不清楚。因此，在最初的GWA研究之外的下一步必须提供有关这些初始关联的基于人群的数据，然后才能将最有希望的发现转化为一般人群的干预，预防和/或治疗方案的改进。国家健康和营养检查调查（NHANES; n〜20,000）的遗传成分可以提供超出最初GWA研究发现所需的数据。 NHANES是一项由疾病控制与预防中心收集的基于美国人群的横断面调查。 NHANES DNA与参与个人的人口，健康，生活方式，实验室，广泛的临床和体格检查数据有关。因为不论健康状况如何，都可以确定参与者，因此NHANES是表型（临床终点和定量性状）和环境暴露的丰富资源。有了这个大型数据集，将描述GWA识别的遗传变异的流行病学结构，并将进行关联研究，以提供更准确的效果大小估计值和人群的可归因于许多常见疾病和特征，例如2型糖尿病，肥胖，肥胖和肥胖，以及肥胖，以及肥胖，以及冠状动脉疾病。最后，将对基因环境和核线粒体基因相互作用进行测试，后者将生成实验室数据以支持统计关联。 这笔赠款的目的是在基于人群的数据集中提供证据，表明GWA认同的遗传变异与大多数人有关。因此，将迅速发布有关GWA识别的变化，基于人群的统计数据和这些变化的修饰符数据，以便研究界可以将最有希望的发现纳入未来的翻译研究中。