Gene-environment interaction in complex disease

复杂疾病中的基因-环境相互作用

• 批准号: 6604428
• 负责人: Molly Bray
• 金额: $ 37.76万
• 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/6604428
• 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）是当今工业化国家的头号死因，是一种复杂的疾病，其病因学涉及多种遗传和环境因素。旨在降低心血管疾病风险和发生率的公共卫生预防计划通常侧重于可改变的环境和行为，例如饮食和体力活动，但效果因人而异。这种对 CVD 干预措施反应的异质性至少部分是遗传起源的。尽管已经确定了许多似乎影响CVD发展的候选基因，但人们对这些遗传效应如何在人口（例如种族和性别）和环境（例如饮食和锻炼）背景下如何变化知之甚少；因此，确定基因和环境如何相互作用以产生 CVD 至关重要。本研究的目的是描述社区动脉粥样硬化风险 (ARIC) 研究中 11,625 名非裔美国人和白人男性和女性的人口样本中 87 个生物和位置候选基因的环境依赖性影响。候选基因座的选择基于已确认的功能意义、与 CVD 或其危险因素的一致关联，和/或在全基因组连锁扫描中确定为位置候选基因座。环境背景将重点关注饮食指标（例如总千卡、Keys 评分、酒精摄入量）、肥胖、体力活动指标（运动、休闲和工作指数）、吸烟和更年期状况/激素使用（仅限女性）。结果变量将包括定量风险因素（例如总胆固醇、BMI、血压）、亚临床疾病（颈动脉壁厚度）和临床疾病（冠心病和中风）的测量。现有的 DNA 样本将用于候选基因座的基因分型，无需与研究参与者进一步联系。由于 ARIC 队列规模庞大，环境和生理测量丰富，为评估可改变环境对遗传变异的影响提供了理想、及时和有效的机会，遗传变异可能影响 CVD 风险和疾病结果，最终目标是建立更有效的 CVD 治疗和预防方案。