Gene-environment interaction in complex disease

复杂疾病中的基因-环境相互作用

• 批准号: 6888978
• 负责人: ERIC A. BOERWINKLE
• 金额: $ 40.87万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-05 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6888978
• 关键词: alcoholic beverage consumption; atherosclerosis; behavioral /social science research tag; blood lipid; blood pressure; body composition; body physical activity; caloric dietary content; cardiovascular disorder risk; clinical research; gene environment interaction; genetic susceptibility; health behavior; human data; human genetic material tag; human middle age (35-64); longitudinal human study; obesity; tobacco abuse

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD), the number one cause of death in industrialized countries today is a complex disease with a multifactorial etiology involving many genetic and environmental factors. Public health prevention programs designed to reduce the risk and occurrence of CVD commonly focus on modifiable environments and behaviors such as diet and physical activity, with varied results among individuals. This heterogeneity in response to CVD interventions is at least in part of genetic origin. Although a number of candidate genes have been identified which appear to influence the development of CVD, little is known about how these genetic effects may vary within demographic (e.g., race and gender) and environmental (e.g., diet and exercise) contexts; thus, it is of utmost importance to determine how genes and environments interact to produce CVD. The purpose of this study is to characterize the environment-dependent effects of 87 biologic and positional candidate genes in a population-based sample of 11,625 African-American and Caucasian men and women from the Atherosclerosis Risk in Communities (ARIC) study. Candidate loci were selected based on confirmed functional significance, consistent association with CVD or its risk factors, and or identified as positional candidates in genome-wide linkage scans. Environmental contexts will focus on dietary measures (e.g., total kcals, Keys score, alcohol intake), obesity, measures of physical activity (sport, leisure, and work indices), smoking, and menopause status/hormone use (women only). Outcome variables will include measures of quantitative risk factors (e.g., total cholesterol, BMI, blood pressure), subclinical disease (carotid wall thickness), and clinical disease (incident CHD and stroke). Existing DNA samples will be used for genotyping of candidate loci, and no further contact with study participants will be necessary. The ARIC cohort, because of its large size and wealth of environmental and physiological measures, provides an ideal, timely, and efficient opportunity to evaluate the effects of modifiable environments on genetic variation which may influence CVD risk and disease outcomes with the ultimate goal of establishing more efficacious programs for the treatment and prevention of CVD.

描述（由申请人提供）：心血管疾病（CVD），当今工业化国家的死亡原因第一，是一种复杂的疾病，具有多因素病因，涉及许多遗传和环境因素。旨在降低CVD的风险和发生的公共卫生预防计划通常集中在可修改的环境和行为上，例如饮食和体育锻炼，并在个人之间产生不同的结果。响应CVD干预措施的这种异质性至少在遗传起源的一部分。尽管已经确定了许多候选基因似乎影响了CVD的发展，但对于这些遗传效应在人口统计学（例如种族和性别）以及环境（例如饮食和锻炼）环境中如何有所不同。因此，确定基因和环境如何相互作用以产生CVD至关重要。这项研究的目的是表征87种生物学和位置候选基因在基于人群的样本中的11,625名非裔美国人和高加索男性和女性的基于人群的基因（ARIC）研究中的男性和女性。根据确认的功能显着性，与CVD或其风险因素的稳定相关性，并在全基因组链接扫描中被确定为位置候选者，选择了候选基因座。环境环境将侧重于饮食措施（例如，总的KCAL，钥匙得分，酒精摄入量），肥胖，体育锻炼的度量（运动，休闲和工作指数），吸烟和更年期的状态/激素使用（仅女性）。结果变量将包括定量危险因素（例如，总胆固醇，BMI，血压），亚临床疾病（颈动脉壁厚）和临床疾病（入射CHD和中风）的度量。现有的DNA样品将用于候选基因座的基因分型，并且不需要与研究参与者进行进一步的接触。 ARIC队列由于其庞大的环境和生理措施，提供了一个理想，及时，有效的机会，以评估可修改环境对遗传变异的影响，这可能会影响CVD风险和疾病结果，其最终目标是确定更有效的程序以治疗和预防CVD。