Genetic & epidemiologic cohort study of asthma & allergy

描述（由申请人提供）：过敏性哮喘、湿疹、花粉热和食物过敏的发病率和严重程度最近急剧增加，特别是在儿童中;美国每四个孩子中就有一个受到影响。这些过敏性疾病的表现是多种多样的，并随着时间的推移而进展。鉴于这种时间上的差异，在单个时间点对儿童进行评估可能无法准确了解过敏性疾病。我们有一个独特的队列，超过1,000名儿童在出生时（1989-1990年）和1岁，2岁，4岁和10岁时患有哮喘和过敏症。使用纵向数据，从这个队列，我们建议确定时间依赖性模式的过敏性疾病，我们术语过敏的轨迹。遗传易感性是哮喘和过敏的关键因素，但我们对这些炎症性疾病易感基因的了解有限。为了更好地了解过敏性哮喘和其他过敏的机制，我们将在从我们的儿童队列收集的DNA样本中研究被认为介导过敏性炎症的候选基因，IL 4，IL 4 R，IL 13，IL 1和IL 1 RN。我们将使用一种新的方法来进行遗传关联研究，通过使用过敏轨迹作为表型，而不是依赖于在单个时间点评估的参数。除了遗传易感性，环境暴露被认为会影响过敏性疾病的存在和严重程度。然而，基因与环境之间相互作用的性质仍不清楚。因此，我们将评估在队列儿童中选定的候选基因和常见的环境暴露之间的基因x环境相互作用。 我们组建了一支经验丰富的多学科研究团队，拥有遗传学，流行病学，临床医学（过敏和免疫学）和生物统计学方面的专业知识。有了这个团队，我们将能够通过扩大哮喘和过敏的流行病学分析，并开始候选基因的遗传关联分析，建立一个全面表征的儿童队列研究人群的坚实基础。通过确定这一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家长提供有关管理实践的宝贵信息，以最大限度地减少易感儿童的风险。

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.