Genetic & epidemiologic cohort study of asthma & allergy

遗传

• 批准号: 7067989
• 负责人: Susan L Ewart
• 金额: $ 39.26万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067989
• 关键词: asthma; atopic dermatitis; child (0-11); clinical chemistry; clinical research; cytokine receptors; gene environment interaction; gene expression; genetic screening; genetic susceptibility; genotype; hay fever; human genetic material tag; human subject; hypersensitivity; interleukin 1; interleukin 13; interleukin 4; linkage disequilibriums; longitudinal human study; respiratory disorder epidemiology; statistics /biometry

DESCRIPTION (provided by applicant): Dramatic increases in the incidence and severity of allergic asthma, eczema, hay fever and food allergy have been seen recently, particularly in children; every fourth child in the U.S. is affected. Manifestations of these allergic diseases are varied and progress over time. Given this chronological variation, the assessment of children at a single time point may not yield an accurate picture of allergic disease. We have a unique cohort of over 1,000 children characterized for asthma and allergy at birth (in 1989-1990) and ages 1, 2, 4, and 10 years. Using longitudinal data from this cohort we propose to identify time-dependent patterns of allergic disorders, which we term allergic trajectories. Genetic predisposition is a key factor underlying asthma and allergy, yet our knowledge of susceptibility genes for these inflammatory disorders is limited. To gain greater understanding of the mechanisms of allergic asthma and other allergies, we will investigate candidate genes thought to mediate allergic inflammation, IL4, IL4R, IL13, IL1 and IL1RN, in DNA samples collected from our cohort of children. We will use a novel approach to perform genetic association studies by using allergic trajectories as phenotypes instead of relying on parameters assessed at a single time point. In addition to genetic susceptibility, environmental exposures are thought to influence both the presence and severity of allergic diseases. However, the nature of the interaction between genes and the environment remains unclear. Thus, we will assess gene x environment interactions between selected candidate genes and common environmental exposures in cohort children. We have assembled a highly experienced multidisciplinary research team with expertise in genetics, epidemiology, clinical medicine (allergy and immunology) and biostatistics. With this team we will be able to build on a strong foundation of a thoroughly characterized childhood cohort study population by expanding the epidemiologic analyses of asthma and allergy, and beginning genetic association analyses of candidate genes. By determining genetic and environmental risk factors in this cohort, we will contribute information valuable to both health care professionals and parents regarding management practices to minimize risks to susceptible children.

描述（由申请人提供）：最近已经看到过敏性哮喘，湿疹，花粉症和食物过敏的发病率和严重程度的急剧增加，尤其是在儿童中；美国每个第四个孩子都受到影响。这些过敏性疾病的表现各不相同，并且会随着时间的流逝而进展。鉴于这种时间顺序的差异，在一个时间点对儿童的评估可能不会产生过敏性疾病的准确情况。我们有一个独特的队列，其中有1,000多名儿童出生时（1989- 1990年）和1、2、4和10岁的出生时有特征。使用该队列中的纵向数据，我们建议确定过敏性疾病的时间依赖性模式，我们将其称为过敏性轨迹。遗传易感性是哮喘和过敏的关键因素，但是我们对这些炎性疾病的易感基因的了解是有限的。为了进一步了解过敏性哮喘和其他过敏的机制，我们将调查被认为介导从我们的儿童同类中收集的DNA样本中的被认为介导过敏性炎症的候选基因，IL4，IL4R，IL13，IL1和IL1RN。我们将使用一种新颖的方法通过使用过敏轨迹作为表型来执行遗传关联研究，而不是依靠在单个时间点评估的参数。除了遗传易感性外，环境暴露还被认为会影响过敏性疾病的存在和严重程度。但是，基因与环境之间相互作用的性质尚不清楚。因此，我们将评估选定候选基因与共同环境暴露儿童中的基因X环境相互作用。 我们组建了一个经验丰富的多学科研究团队，该团队在遗传学，流行病学，临床医学（过敏和免疫学）和生物统计学方面具有专业知识。在这个团队中，我们将能够通过扩大哮喘和过敏的流行病学分析，并开始对候选基因的遗传关联分析来建立彻底表征的童年研究人群的牢固基础。通过确定该队列中的遗传和环境风险因素，我们将为医疗保健专业人员和父母提供有关管理实践的有价值的信息，以最大程度地降低易感儿童的风险。