Genome-wide interactions with diet patterns on long-term weight change

描述（由申请人提供）： 肥胖和体重增加是心血管疾病（CVD）的主要可改变的危险因素，在过去的几十年中，肥胖的患病率一直在惊人地增加。饮食是影响肥胖流行的最重要的环境因素之一，可能与基因组变异相互作用。然而，目前还没有关于基因-饮食相互作用的全基因组研究报道，并且以前的基因-饮食相互作用研究在设计和分析策略上存在严重缺陷。本申请的目的是在美国肥胖症迅速增加的时期（~1980-2000），对基因-饮食相互作用对肥胖性状（体重指数，BMI;和腰臀比，WHR）长期变化的影响进行新的全基因组分析，并应用最先进的方法克服该领域的主要挑战。我们将使用新开发的“方差优先化”程序来选择对与环境的相互作用敏感的遗传变体（Ai 1）;并在五个前瞻性队列中检查优先化的遗传变体与总体饮食模式/质量指数之间的相互作用，所述五个前瞻性队列包括来自DietGen和CHARGE Consortia的总共约59，000名美国男性和女性（Aim 2）。由于所有研究对象都可以获得饮食摄入量、肥胖特征和全基因组扫描的信息，因此拟议的项目将以极具成本效益的方式进行。我们聚集了一批经验丰富的合作者，他们在流行病学，遗传学，统计学，基因-环境相互作用和营养学方面具有专业知识。我们相信，这项无与伦比的研究结果将提供一个独特的机会，以确定新的基因-饮食相互作用对肥胖的流行，并促进饮食调整预防和治疗肥胖和心血管疾病。

DESCRIPTION (provided by applicant): Obesity and weight gain are major modifiable risk factors for cardiovascular disease (CVD), and the prevalence of obesity has been increasing alarmingly in the past decades. Diet is among the most important environmental factors that may interact with genomic variations in affecting obesity epidemic. However, no genome-wide study on gene-diet interactions has been reported, and previous gene-diet interaction studies are severely flawed in design and analytic strategies. The goal of this application is to conduct novel, genome-wide analyses of gene-diet interactions on long-term changes in obesity traits (body mass index, BMI; and waist to hip ratio, WHR) in the period of time when obesity rapidly increased in the United States (~1980-2000), and apply state-of-the-art approaches to overcome the major challenges in the field. We will use the newly- developed 'variance prioritization' procedure to select genetic variants sensitive to interactions with environment (Ai 1); and examine interactions between the prioritized genetic variants and overall diet patterns/quality indices in five prospective cohorts including in total ~59,000 US men and women from the DietGen and CHARGE Consortia (Aim 2). Because information of dietary intakes, obesity traits, and genome- wide scans are available in all the cohorts, the proposed project will be conducted in an extremely cost-efficient manner. We have assembled a solid group of experienced collaborators with expertise in epidemiology, genetics, statistics, gene-environment interactions, and nutrition. We believe that findings of this unparalleled study will provide a unique opportunity to identify novel gene-diet interactions on obesity epidemic, and promote diet modifications on prevention and treatment of obesity and CVD.